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<article doi="10.1002/emmm.201302771" abstract="Tyrosine kinase inhibitors (TKIs) are effective therapies for leukaemia. Alzheimer is a neurodegenerative disease characterized by accumulation of β-amyloid (plaques) and hyper-phosphorylated Tau (tangles). Here we show that AD animals have high levels of insoluble parkin and decreased parkin-Beclin-1 interaction, while peripheral administration of TKIs, including Nilotinib and Bosutinib, increases soluble parkin leading to amyloid clearance and cognitive improvement. Blocking Beclin-1 expression with shRNA or parkin deletion prevents tyrosine kinase (TK) inhibition-induced amyloid clearance, suggesting that functional parkin-Beclin-1 interaction mediates amyloid degradation. Isolation of autophagic vacuoles (AVs) in AD mouse brain shows accumulation of parkin and amyloid, consistent with previous results in AD brains, while Bosutinib and Nilotinib increase parkin-Beclin-1 interaction and result in protein deposition in the lysosome. These data suggest that decreased parkin solubility impedes parkin-Beclin-1 interaction and amyloid clearance. We identified two FDA-approved anti-cancer drugs as potential treatment for AD."><fig id="181"><title></title><label>Figure 1</label><graphic href="https://api.sourcedata.io/file.php?figure_id=181"/><sd-panel panel_id="16020"><p>Graph represents <sd-tag id="sdTag88" source="sdapi" category="entity" entity_type="tissue" role="assayed" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> levels of TKIs over a 24 hr period after IP injection with <sd-tag id="sdTag89" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Imatinib" ext_ids="CHEBI:38918" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Imatinib</sd-tag>, <sd-tag id="sdTag90" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Nilotinib" ext_ids="CHEBI:52172" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="nilotinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Nilotinib</sd-tag>, <sd-tag id="sdTag91" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> and <sd-tag id="sdTag92" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> (N = 7). [Correction added after publication on 4 July 2013: The y axis of the graph shown in Fig. 1A has been corrected from "concentration (mM)" to "concentration (nM)"]</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16020"/></sd-panel><sd-panel panel_id="16021"><p><sd-tag id="sdTag100" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> in Tg-<sd-tag id="sdTag101" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> total <sd-tag id="sdTag102" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> lysates on 4-12% <sd-tag id="sdTag334" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> (Invitrogen) show total <sd-tag id="sdTag104" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Abl" ext_ids="Q4JIM5///P00520" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Abl2///Abl1" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Abl</sd-tag> (top blot) T412 <sd-tag id="sdTag107" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Abl" ext_ids="Q4JIM5///P00520" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Abl2///Abl1" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Abl</sd-tag> (2<sup>nd</sup> blot), soluble <sd-tag id="sdTag103" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> level (3<sup>rd</sup> blot), and <sd-tag id="sdTag105" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> (4<sup>th</sup> blot) relative to <sd-tag id="sdTag106" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="MAP-2" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">MAP-2</sd-tag> (N = 9).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16021"/></sd-panel><sd-panel panel_id="16022"><p>Quantitative <sd-tag id="sdTag112" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> showing soluble (STEN extract) and insoluble (4 M urea extract) <sd-tag id="sdTag113" source="sdapi" category="entity" entity_type="organism" role="component" text="mouse" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mouse</sd-tag><sd-tag id="sdTag114" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> in Tg-<sd-tag id="sdTag115" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> (N = 9). <sd-tag id="sdTag111" source="sdapi" category="entity" entity_type="gene" role="component" text="Parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Parkin</sd-tag><sup>−/−</sup><sd-tag id="sdTag116" source="sdapi" category="entity" entity_type="tissue" role="component" text="brains" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brains</sd-tag> were used as a specificity control.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16022"/></sd-panel><sd-panel panel_id="16023"><p>(D) <sd-tag id="sdTag123" source="sdapi" category="assay" entity_type="" role="" text="Blots" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Blots</sd-tag> represent <sd-tag id="sdTag122" source="sdapi" category="assay" entity_type="" role="" text="immunoprecipitated" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoprecipitated</sd-tag><sd-tag id="sdTag119" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin-1" ext_ids="O88597" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Becn1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Beclin-1</sd-tag> in <sd-tag id="sdTag120" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> probed with <sd-tag id="sdTag121" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> antibody</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16023"/></sd-panel><sd-panel panel_id="16024"><p>(D) <sd-tag id="sdTag132" source="sdapi" category="assay" entity_type="" role="" text="Blots" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Blots</sd-tag> represent <sd-tag id="sdTag133" source="sdapi" category="assay" entity_type="" role="" text="immunoprecipitated" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoprecipitated</sd-tag><sd-tag id="sdTag134" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin-1" ext_ids="O88597" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Becn1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Beclin-1</sd-tag> in <sd-tag id="sdTag135" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> probed with <sd-tag id="sdTag136" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> antibody, and (E) control <sd-tag id="sdTag131" source="sdapi" category="entity" entity_type="subcellular" role="component" text="IgG" ext_ids="GO:0071735" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="IgG immunoglobulin complex" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">IgG</sd-tag> in parallel with immunoprecipitates.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16024"/></sd-panel><sd-panel panel_id="16025"><p>(F) <sd-tag id="sdTag141" source="sdapi" category="assay" entity_type="" role="" text="immunoprecipitated" ext_ids="BAO_0002508" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="immunoprecipitation" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">immunoprecipitated</sd-tag><sd-tag id="sdTag142" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin-1" ext_ids="Q14457" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">Beclin-1</sd-tag> probed with <sd-tag id="sdTag143" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="O60260" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="PARK2" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> and the reverse experiment in post-mortem <sd-tag id="sdTag144" source="sdapi" category="entity" entity_type="organism" role="experiment" text="human" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">human</sd-tag> AD <sd-tag id="sdTag145" source="sdapi" category="entity" entity_type="tissue" role="component" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> analyzed on 4-12% <sd-tag id="sdTag335" source="sdapi" category="assay" entity_type="" role="" text="SDS-NuPAGE gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">SDS-NuPAGE gel</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16025"/></sd-panel><sd-panel panel_id="16027"><p>In situ <sd-tag id="sdTag148" source="sdapi" category="assay" entity_type="" role="" text="proximity ligation assay" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">proximity ligation assay</sd-tag> (<sd-tag id="sdTag151" source="sdapi" category="assay" entity_type="" role="" text="PLA" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">PLA</sd-tag>) shows endogenous <sd-tag id="sdTag152" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag>-<sd-tag id="sdTag153" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin-1" ext_ids="O88597" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Becn1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Beclin-1</sd-tag> complexes in (G) WT <sd-tag id="sdTag149" source="sdapi" category="entity" entity_type="organism" role="component" text="C57BL/6" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">C57BL/6</sd-tag><sd-tag id="sdTag154" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> (N = 5) and (H) <sd-tag id="sdTag161" source="sdapi" category="entity" entity_type="gene" role="component" text="parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">parkin</sd-tag><sup>−/−</sup> as control.</p><p><sd-tag id="sdTag150" source="sdapi" category="assay" entity_type="" role="" text="PLA" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">PLA</sd-tag> in Tg-<sd-tag id="sdTag156" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag157" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> IP injected once daily for 3 weeks with (I) <sd-tag id="sdTag158" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> (J) 5 mg/kg <sd-tag id="sdTag159" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> and (K) 10 mg/kg <sd-tag id="sdTag160" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Nilotinib" ext_ids="CHEBI:52172" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="nilotinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Nilotinib</sd-tag> (N = 5).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16027"/></sd-panel><sd-panel panel_id="16028"><p><sd-tag id="sdTag168" source="sdapi" category="assay" entity_type="" role="" text="PLA" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">PLA</sd-tag> in <sd-tag id="sdTag169" source="sdapi" category="entity" entity_type="organism" role="component" text="human" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">human</sd-tag> post-mortem <sd-tag id="sdTag170" source="sdapi" category="entity" entity_type="tissue" role="component" text="brains" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brains</sd-tag> in the (L) <sd-tag id="sdTag171" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of a normal subject and (M) <sd-tag id="sdTag172" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of an AD <sd-tag id="sdTag174" source="sdapi" category="entity" entity_type="organism" role="experiment" text="patient" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">patient</sd-tag>; the <sd-tag id="sdTag166" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="hippocampus" ext_ids="UBERON:0002421" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="hippocampal formation" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">hippocampus</sd-tag> of (N) a normal subject and (O) an AD <sd-tag id="sdTag173" source="sdapi" category="entity" entity_type="organism" role="experiment" text="patient" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">patient</sd-tag>; the <sd-tag id="sdTag167" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="caudate" ext_ids="UBERON:0001873" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="caudate nucleus" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">caudate</sd-tag> of (P) a normal subject and (Q) an AD <sd-tag id="sdTag175" source="sdapi" category="entity" entity_type="organism" role="experiment" text="patient" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">patient</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16028"/></sd-panel><sd-panel panel_id="16029">Graph represents <sd-tag id="sdTag185" source="sdapi" category="entity" entity_type="organism" role="component" text="human" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">human</sd-tag> <span><sd-tag id="sdTag181" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag></span><sub>1-42</sub><sd-tag id="sdTag186" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> <span>in rat <sd-tag id="sdTag182" source="sdapi" category="entity" entity_type="cell_line" role="component" text="B35" ext_ids="CVCL_1951" norm_text="" ext_dbs="CVCL" in_caption="True" ext_names="B35" ext_tax_ids="10116" ext_tax_names="Rattus norvegicus" ext_urls="https://identifiers.org/cellosaurus:">B35</sd-tag> neuroblastoma cells transfected with</span> <sd-tag id="sdTag187" source="sdapi" category="entity" entity_type="organism" role="component" text="human" ext_ids="9606" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Homo sapiens" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">human</sd-tag> <span>cDNA <sd-tag id="sdTag183" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Aβ" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/"></sd-tag></span><sub>1-42</sub> (or LacZ) or <span><sd-tag id="sdTag184" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Beclin-1" ext_ids="8678" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="BECN1" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">Beclin-1</sd-tag></span> shRNA for 24 hr, and then treated with 1 μM <sd-tag id="sdTag188" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> for an additional 24 hr (N = 12). *Significantly different to control or as indicated, Mean ± SEM, ANOVA with NeumannKeuls multiple comparison.<graphic href="https://api.sourcedata.io/file.php?panel_id=16029"/></sd-panel></fig><fig id="182"><title></title><label>Figure 2</label><graphic href="https://api.sourcedata.io/file.php?figure_id=182"/><sd-panel panel_id="896"><p>Staining of 20 μm <sd-tag id="sdTag194" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> sections shows <sd-tag id="sdTag201" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="plaque" ext_ids="GO:0097418" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="neurofibrillary tangle" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">plaque</sd-tag> formation with <sd-tag id="sdTag192" source="sdapi" category="assay" entity_type="" role="" text="6E10" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">6E10</sd-tag> antibody and <sd-tag id="sdTag193" source="sdapi" category="assay" entity_type="" role="" text="DAB" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">DAB</sd-tag> in the <sd-tag id="sdTag195" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> in different (A,B) Tg-<sd-tag id="sdTag196" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> + <sd-tag id="sdTag189" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> and (C) <sd-tag id="sdTag190" source="sdapi" category="assay" entity_type="" role="" text="thioflavin-S" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">thioflavin-S</sd-tag> staining in Tg-<sd-tag id="sdTag197" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> treated with <sd-tag id="sdTag198" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> (N = 7). (D,E) Tg-<sd-tag id="sdTag199" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> treated with 5 mg/kg <sd-tag id="sdTag200" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> for 3-weeks and (F) <sd-tag id="sdTag191" source="sdapi" category="assay" entity_type="" role="" text="thioflavin-s" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">thioflavin-s</sd-tag> staining.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=896"/></sd-panel><sd-panel panel_id="16030"><p>Staining of 20 μm thick <sd-tag id="sdTag204" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> sections shows (G) <sd-tag id="sdTag205" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag>, (H) <sd-tag id="sdTag206" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (I) merged figure in <sd-tag id="sdTag207" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of Tg-<sd-tag id="sdTag208" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag209" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> after 3 weeks of <sd-tag id="sdTag210" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> treatment, and (J) <sd-tag id="sdTag211" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag>, (K) <sd-tag id="sdTag212" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (L) merged figure in <sd-tag id="sdTag213" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of Tg-<sd-tag id="sdTag214" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag215" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> after 3 weeks of 5 mg/kg <sd-tag id="sdTag216" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> treatment. (M) <sd-tag id="sdTag229" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Parkin</sd-tag>, (N) <sd-tag id="sdTag218" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (O) merged figure in <sd-tag id="sdTag219" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="hippocampus" ext_ids="UBERON:0002421" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="hippocampal formation" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">hippocampus</sd-tag> of Tg-<sd-tag id="sdTag220" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag221" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> after 3 weeks of <sd-tag id="sdTag222" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> treatment, and (P) <sd-tag id="sdTag223" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag>, (Q) <sd-tag id="sdTag224" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (R) merged figure in <sd-tag id="sdTag225" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of Tg-<sd-tag id="sdTag226" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag227" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> after 3 weeks of <sd-tag id="sdTag228" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> treatment (N = 7).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16030"/></sd-panel><sd-panel panel_id="16032"><span>(S) Graphs represent quantification of <sd-tag id="sdTag231" source="sdapi" category="entity" entity_type="protein" role="assayed" text="amyloid" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">amyloid</sd-tag><sd-tag id="sdTag232" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="plaques" ext_ids="GO:0097418" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="neurofibrillary tangle" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">plaques</sd-tag> in Tg-</span><sd-tag id="sdTag233" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> with and without <sd-tag id="sdTag234" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag>.<graphic href="https://api.sourcedata.io/file.php?panel_id=16032"/></sd-panel><sd-panel panel_id="16033"><sd-tag id="sdTag241" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> in Tg-<sd-tag id="sdTag242" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> total <sd-tag id="sdTag243" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> <span>lysates on 4-12% <sd-tag id="sdTag336" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> (Invitrogen) showing (T) levels of <sd-tag id="sdTag238" source="sdapi" category="entity" entity_type="protein" role="assayed" text="BACE1" ext_ids="P56818" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Bace1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">BACE1</sd-tag> (1</span><sup>st</sup> <span>blot), <sd-tag id="sdTag239" source="sdapi" category="entity" entity_type="protein" role="assayed" text="ADAM-10" ext_ids="O35598" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Adam10" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">ADAM-10</sd-tag> (2</span><sup>nd</sup> <span>blot) and <sd-tag id="sdTag240" source="sdapi" category="entity" entity_type="protein" role="assayed" text="presinilin-1" ext_ids="P49769" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Psen1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">presinilin-1</sd-tag> (3</span><sup>rd</sup> blot) relative to <sd-tag id="sdTag244" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">actin</sd-tag><graphic href="https://api.sourcedata.io/file.php?panel_id=16033"/></sd-panel><sd-panel panel_id="16034"><sd-tag id="sdTag250" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> in Tg-<sd-tag id="sdTag251" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> total <sd-tag id="sdTag252" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> <span>lysates on 4-12% <sd-tag id="sdTag337" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> (Invitrogen) showing (U) total</span> <sd-tag id="sdTag253" source="sdapi" category="entity" entity_type="protein" role="assayed" text="APP" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/">APP</sd-tag> (top blot), CTFs (2<sup>nd</sup> blot) and phospho-tyrosine (3<sup>rd</sup> blot) relative to <sd-tag id="sdTag254" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">actin</sd-tag> (N = 9).<graphic href="https://api.sourcedata.io/file.php?panel_id=16034"/></sd-panel></fig><fig id="183"><title></title><label>Figure 3</label><graphic href="https://api.sourcedata.io/file.php?figure_id=183"/><sd-panel panel_id="16048"><p>Graphs represent <sd-tag id="sdTag259" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> of human <sd-tag id="sdTag260" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> in (A) <sd-tag id="sdTag261" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> levels and (B) <sd-tag id="sdTag258" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="blood" ext_ids="UBERON:0000178" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="blood" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">blood</sd-tag><sd-tag id="sdTag262" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> levels in 8-month old Tg-<sd-tag id="sdTag266" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag263" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> injected I.P. every other day for 6 weeks with <sd-tag id="sdTag264" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> or <sd-tag id="sdTag265" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Nilotinib" ext_ids="CHEBI:52172" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="nilotinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Nilotinib</sd-tag> (N = 10).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16048"/></sd-panel><sd-panel panel_id="16049"><p><sd-tag id="sdTag267" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> of human soluble and insoluble <sd-tag id="sdTag269" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> (C) <sd-tag id="sdTag270" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (D) <sd-tag id="sdTag271" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-40</sub> levels in 8-month old Tg-<sd-tag id="sdTag272" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag273" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> injected IP daily for 3 weeks with 5 mg/kg <sd-tag id="sdTag274" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> (N = 9).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16049"/></sd-panel><sd-panel panel_id="16040"><sd-tag id="sdTag276" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> of (E) <sd-tag id="sdTag277" source="sdapi" category="entity" entity_type="organism" role="component" text="mouse" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mouse</sd-tag> <span>p-<sd-tag id="sdTag281" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> levels in 8-month old Tg-</span><sd-tag id="sdTag278" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> <sd-tag id="sdTag279" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> injected IP daily for 3 weeks with 5 mg/kg <sd-tag id="sdTag280" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> (N = 9).<graphic href="https://api.sourcedata.io/file.php?panel_id=16040"/></sd-panel><sd-panel panel_id="16041"><sd-tag id="sdTag283" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> in Tg-<sd-tag id="sdTag284" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> total <sd-tag id="sdTag285" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> <span>lysates on 4-12% <sd-tag id="sdTag338" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> (Invitrogen) show total</span> <sd-tag id="sdTag286" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> (1<sup>st</sup> blot), serine 396 p-<sd-tag id="sdTag287" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> (2<sup>nd</sup> blot), threonine 231 (AT180, 3<sup>rd</sup> blot) and serine 199 p-<sd-tag id="sdTag288" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> (AT8, 4<sup>th</sup> blot) relative to <sd-tag id="sdTag289" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">actin</sd-tag> (N = 7).<graphic href="https://api.sourcedata.io/file.php?panel_id=16041"/></sd-panel></fig><fig id="184"><title></title><label>Figure 4</label><graphic href="https://api.sourcedata.io/file.php?figure_id=184"/><sd-panel panel_id="16042"><p>Staining of 20μm <sd-tag id="sdTag293" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> sections shows intracellular <sd-tag id="sdTag294" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> within the (A) <sd-tag id="sdTag295" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="hippocampus" ext_ids="UBERON:0002421" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="hippocampal formation" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">hippocampus</sd-tag> of <sd-tag id="sdTag296" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag297" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> injected WT <sd-tag id="sdTag298" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag>, and (B) <sd-tag id="sdTag299" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> clearance of intracellular <sd-tag id="sdTag300" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub>. Staining of 20μm <sd-tag id="sdTag339" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> sections shows intracellular <sd-tag id="sdTag301" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> within the (C) <sd-tag id="sdTag302" source="sdapi" category="entity" entity_type="tissue" role="experiment" text="cortex" ext_ids="UBERON:0002129" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="cerebellar cortex" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">cortex</sd-tag> of WT <sd-tag id="sdTag303" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> with the <sd-tag id="sdTag304" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag305" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub>, and (D) <sd-tag id="sdTag306" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> clearance of intracellular <sd-tag id="sdTag307" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> (N = 7).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16042"/></sd-panel><sd-panel panel_id="16043"><sd-tag id="sdTag312" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> of human soluble and insoluble <sd-tag id="sdTag313" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> at 6 weeks post-injection of <sd-tag id="sdTag314" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag315" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and daily treatment with 5 mg/kg <sd-tag id="sdTag316" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> (N = 9) for 3 weeks. * Significantly different to control or as indicated, Mean ± SEM, ANOVA with Neumann Keuls multiple comparison.<graphic href="https://api.sourcedata.io/file.php?panel_id=16043"/></sd-panel><sd-panel panel_id="16044"><sd-tag id="sdTag321" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> <span>on 4-12% <sd-tag id="sdTag333" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> of total</span> <sd-tag id="sdTag322" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> lysates in 1 year old wild type and <span><sd-tag id="sdTag320" source="sdapi" category="entity" entity_type="gene" role="intervention" text="parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">parkin</sd-tag></span><sup>−/−</sup><sd-tag id="sdTag323" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> treated with 5 mg/kg <sd-tag id="sdTag324" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> <span>for 3 weeks on 4-12% <sd-tag id="sdTag340" source="sdapi" category="assay" entity_type="" role="" text="NuPAGE SDS gel" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">NuPAGE SDS gel</sd-tag> (Invitrogen) showing</span> <sd-tag id="sdTag325" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag> (1<sup>st</sup> blot)total <sd-tag id="sdTag326" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Abl" ext_ids="P00520///Q4JIM5" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Abl1///Abl2" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Abl</sd-tag> (2<sup>nd</sup> blot), T412 <sd-tag id="sdTag327" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Abl" ext_ids="P00520///Q4JIM5" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Abl1///Abl2" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">Abl</sd-tag> (3<sup>rd</sup> blot), <sd-tag id="sdTag328" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Beclin-1" ext_ids="O88597" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Becn1" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Beclin-1</sd-tag> (4th blot) and <sd-tag id="sdTag329" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3" ext_ids="Q91VR7///Q9CQV6" norm_text="" ext_dbs="Uniprot///Uniprot" in_caption="True" ext_names="Map1lc3a///Map1lc3b" ext_tax_ids="10090///10090" ext_tax_names="Mus musculus///Mus musculus" ext_urls="https://www.uniprot.org/uniprot////https://www.uniprot.org/uniprot/">LC3</sd-tag> (5<sup>th</sup> blot) relative to <sd-tag id="sdTag330" source="sdapi" category="entity" entity_type="protein" role="normalizing" text="actin" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">actin</sd-tag> (N = 7).<graphic href="https://api.sourcedata.io/file.php?panel_id=16044"/></sd-panel><sd-panel panel_id="16045"><p>Staining of 20μm <sd-tag id="sdTag344" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> sections shows <sd-tag id="sdTag345" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="plaque" ext_ids="GO:0097418" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="neurofibrillary tangle" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">plaque</sd-tag> formation with <sd-tag id="sdTag346" source="sdapi" category="assay" entity_type="" role="" text="6E10" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">6E10</sd-tag> antibody and <sd-tag id="sdTag347" source="sdapi" category="assay" entity_type="" role="" text="DAB" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">DAB</sd-tag> 6 weeks post-injection with (G) <sd-tag id="sdTag348" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag349" source="sdapi" category="entity" entity_type="protein" role="component" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> + 3 weeks <sd-tag id="sdTag350" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> treatment and (H) IP injection with 5 mg/kg <sd-tag id="sdTag351" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> 3 weeks post-<sd-tag id="sdTag352" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag> expression (3 weeks treatment) clears <sd-tag id="sdTag353" source="sdapi" category="entity" entity_type="subcellular" role="assayed" text="plaques" ext_ids="GO:0097418" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="neurofibrillary tangle" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">plaques</sd-tag> in WT <sd-tag id="sdTag354" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> (N = 7).(I) Lentiviral <sd-tag id="sdTag355" source="sdapi" category="entity" entity_type="protein" role="component" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> + <sd-tag id="sdTag356" source="sdapi" category="entity" entity_type="molecule" role="component" text="DMSO" ext_ids="CHEBI:4612" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">DMSO</sd-tag> and (J) IP injection with 5 mg/kg <sd-tag id="sdTag357" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> 3 weeks post-<sd-tag id="sdTag358" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag> expression (3 weeks treatment) in <sd-tag id="sdTag361" source="sdapi" category="entity" entity_type="gene" role="intervention" text="parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">parkin</sd-tag><sup>−/−</sup><sd-tag id="sdTag360" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> (N = 7).</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16045"/></sd-panel></fig><fig id="185"><title></title><label>Figure 5</label><graphic href="https://api.sourcedata.io/file.php?figure_id=185"/><sd-panel panel_id="16046"><p>Graphs represent <sd-tag id="sdTag367" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> (N = 5) in <sd-tag id="sdTag365" source="sdapi" category="entity" entity_type="subcellular" role="experiment" text="autophagic vacuoles" ext_ids="GO:0005776" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autophagic vacuole" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">autophagic vacuoles</sd-tag> (<sd-tag id="sdTag387" source="sdapi" category="entity" entity_type="subcellular" role="experiment" text="AVs" ext_ids="GO:0005776" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autophagic vacuole" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">AVs</sd-tag>) in the <sd-tag id="sdTag368" source="sdapi" category="entity" entity_type="tissue" role="component" text="brain" ext_ids="UBERON:0000955" norm_text="" ext_dbs="Uberon" in_caption="True" ext_names="brain" ext_tax_ids="" ext_tax_names="" ext_urls="https://www.ebi.ac.uk/ols/ontologies/uberon/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FUBERON_">brain</sd-tag> of 4 and 8 months old Tg-<sd-tag id="sdTag369" source="sdapi" category="entity" entity_type="gene" role="component" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag><sd-tag id="sdTag370" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> treated with 10 mg/kg <sd-tag id="sdTag371" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Nilotinib" ext_ids="CHEBI:52172" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="nilotinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Nilotinib</sd-tag> or 5 mg/kg <sd-tag id="sdTag372" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> (N = 5) for 3 weeks showing (A)human<sd-tag id="sdTag374" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> (Insert is <sd-tag id="sdTag375" source="sdapi" category="assay" entity_type="" role="" text="WB" ext_ids="BAO_0002424" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="western blot" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">WB</sd-tag> analysis of <sd-tag id="sdTag388" source="sdapi" category="entity" entity_type="subcellular" role="experiment" text="AVs" ext_ids="GO:0005776" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autophagic vacuole" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">AVs</sd-tag> showing <sd-tag id="sdTag381" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LC3-B" ext_ids="Q9CQV6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Map1lc3b" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">LC3-B</sd-tag> in AV10 and AV20 (1<sup>st</sup> blot) and <sd-tag id="sdTag382" source="sdapi" category="entity" entity_type="protein" role="assayed" text="LAMP2a" ext_ids="P17047" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Lamp2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">LAMP2a</sd-tag> in Lys (2<sup>nd</sup> blot) fraction) and (B)<sd-tag id="sdTag378" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-40</sub>,(C) p-<sd-tag id="sdTag379" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> and (D) <sd-tag id="sdTag380" source="sdapi" category="entity" entity_type="protein" role="assayed" text="parkin" ext_ids="Q9WVS6" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">parkin</sd-tag>.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16046"/></sd-panel><sd-panel panel_id="16047"><p><sd-tag id="sdTag391" source="sdapi" category="assay" entity_type="" role="" text="ELISA" ext_ids="BAO_0000134" norm_text="" ext_dbs="BAO" in_caption="True" ext_names="ELISA" ext_tax_ids="" ext_tax_names="" ext_urls="https://bioportal.bioontology.org/ontologies/BAO/?p=classes&amp;conceptid=http%3A%2F%2Fwww.bioassayontology.org%2Fbao%23">ELISA</sd-tag> in <sd-tag id="sdTag392" source="sdapi" category="entity" entity_type="subcellular" role="experiment" text="autophagic vacuoles" ext_ids="GO:0005776" norm_text="" ext_dbs="Gene Ontology" in_caption="True" ext_names="autophagic vacuole" ext_tax_ids="" ext_tax_names="" ext_urls="http://amigo.geneontology.org/amigo/term/">autophagic vacuoles</sd-tag> of 1 year old WT and <sd-tag id="sdTag399" source="sdapi" category="entity" entity_type="gene" role="intervention" text="parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">parkin</sd-tag><sup>−/−</sup><sd-tag id="sdTag394" source="sdapi" category="entity" entity_type="organism" role="component" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag> (N = 5) injected with <sd-tag id="sdTag389" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag390" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> for 3 weeks and treated with 10 mg/kg <sd-tag id="sdTag395" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Nilotinib" ext_ids="CHEBI:52172" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="nilotinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Nilotinib</sd-tag> and 5 mg/kg <sd-tag id="sdTag396" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> for 3 additional weeks showing (E) human<sd-tag id="sdTag397" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Aβ" ext_ids="P05067" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="https://www.uniprot.org/uniprot/"></sd-tag><sub>1-42</sub> and (F) p-<sd-tag id="sdTag398" source="sdapi" category="entity" entity_type="protein" role="assayed" text="Tau" ext_ids="P10637" norm_text="" ext_dbs="Uniprot" in_caption="True" ext_names="Mapt" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="https://www.uniprot.org/uniprot/">Tau</sd-tag> levels.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16047"/></sd-panel></fig><fig id="186"><title></title><label>Figure 6</label><graphic href="https://api.sourcedata.io/file.php?figure_id=186"/><sd-panel panel_id="16076"><p>(A) Represents results of <sd-tag id="sdTag404" source="sdapi" category="assay" entity_type="" role="" text="Morris water maze" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Morris water maze</sd-tag> test in <sd-tag id="sdTag405" source="sdapi" category="entity" entity_type="organism" role="component" text="lentiviral" ext_ids="11646" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Lentivirus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">lentiviral</sd-tag><sd-tag id="sdTag406" source="sdapi" category="entity" entity_type="gene" role="intervention" text="Aβ" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/"></sd-tag><sub>1-42</sub>-injected ± <sd-tag id="sdTag407" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> WT (N = 12) and <sd-tag id="sdTag408" source="sdapi" category="entity" entity_type="gene" role="intervention" text="parkin" ext_ids="50873" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="Park2" ext_tax_ids="10090" ext_tax_names="Mus musculus" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">parkin</sd-tag><sup>−/−</sup> (N = 10) <sd-tag id="sdTag409" source="sdapi" category="entity" entity_type="organism" role="assayed" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag>, and (B) <sd-tag id="sdTag410" source="sdapi" category="assay" entity_type="" role="" text="heat maps" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">heat maps</sd-tag> for each group.</p><p>Graphs represent total number of entry into platform area and distance travelled.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16076"/></sd-panel><sd-panel panel_id="16077"><p>Represents results of <sd-tag id="sdTag412" source="sdapi" category="assay" entity_type="" role="" text="Morris water maze" ext_ids="" norm_text="" ext_dbs="" in_caption="True" ext_names="" ext_tax_ids="" ext_tax_names="" ext_urls="">Morris water maze</sd-tag> test in Tg-<sd-tag id="sdTag413" source="sdapi" category="entity" entity_type="gene" role="intervention" text="APP" ext_ids="351" norm_text="" ext_dbs="NCBI gene" in_caption="True" ext_names="APP" ext_tax_ids="9606" ext_tax_names="Homo sapiens" ext_urls="http://www.ncbi.nlm.nih.gov/gene/">APP</sd-tag> ± <sd-tag id="sdTag414" source="sdapi" category="entity" entity_type="molecule" role="intervention" text="Bosutinib" ext_ids="CHEBI:39112" norm_text="" ext_dbs="ChEBI" in_caption="True" ext_names="bosutinib" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ebi.ac.uk/chebi/searchId.do?chebiId=">Bosutinib</sd-tag> (N = 12) <sd-tag id="sdTag415" source="sdapi" category="entity" entity_type="organism" role="assayed" text="mice" ext_ids="10090" norm_text="" ext_dbs="NCBI taxon" in_caption="True" ext_names="Mus musculus" ext_tax_ids="" ext_tax_names="" ext_urls="http://www.ncbi.nlm.nih.gov/taxonomy/">mice</sd-tag>.</p><p>Graphs represent total number of entry into platform area and distance travelled.</p><graphic href="https://api.sourcedata.io/file.php?panel_id=16077"/></sd-panel></fig></article>