PMCID string | Title string | Sentences string |
|---|---|---|
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Alternative or complementary mechanisms may also contribute to AT8 depletion, which are discussed in the following paragraph. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While ageing is an important factor to consider when interpreting changes in AT8 localisation, our findings support the hypothesis that the alterations observed in AD are not solely age-related. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Notably, the older control group (63–68 years old) did not exhibit a comparable depletion of nuclear AT8 to that observed in AD stages. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | It should be noted that the number of human post-mortem samples analysed in this study was limited, which may constrain the generalisation of the observed trends. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Nevertheless, the consistency of AT8 nuclear depletion across independent specimens supports the robustness of these findings. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Consistent with previous studies showing that ageing can predispose neurons to tau pathology by promoting chromatin relaxation and transcriptional instability , our data suggest that early AD stages may act synergistically with ageing to exacerbate the loss of nuclear AT8, a phenomenon that becomes more pronounced as the disease progresses. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Collectively, these findings point to a disease-specific vulnerability that extends beyond chronological ageing and reflects a combination of age-related chromatin dysregulation and early AD-associated nuclear alterations, including aberrant reactivation of the cell cycle in post-mitotic neurons. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The correlation between AT8 loss and neuronal degeneration suggests that nuclear AT8 may play a protective role under physiological conditions. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, its depletion could predispose neurons to aberrant cell cycle re-entry. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Previous studies have shown that neuroblastoma cells can be induced to re-enter the cell cycle upon exposure to forskolin or aniline, which coincides with the loss of nuclear AT8 and increased cyclin expression . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In mature neurons, which are post-mitotic, inappropriate reactivation of the cell cycle may result in cellular stress and contribute to neurodegeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Interestingly, in hippocampal tissue from AD patients, we identified Ki67-positive neurons that also retained nuclear AT8 staining, while other AT8-positive neurons were Ki67-negative. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | This distribution does not suggest a strictly inverse relationship between the two markers. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Instead, it indicates that nuclear AT8 and cell cycle reactivation can coexist in vulnerable neurons. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | These observations suggest that while nuclear AT8 may support neuronal stability under normal conditions, its persistence during replicative stress may reflect a dysfunctional nuclear state that contributes to degeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Our co-localisation data align with previous reports describing ectopic expression of Ki67 and cyclins in post-mitotic neurons during neurodegeneration . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Importantly, neuroblastoma cells and mature neurons may differ in their response to proliferative stimuli and nuclear AT8 dynamics. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While cell cycle reactivation in neuroblastoma cells typically correlates with decreased nuclear AT8, in aged or AD neurons, AT8 may persist despite the presence of proliferation markers. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Alternative mechanisms could also contribute to the observed depletion of AT8 in vulnerable neurons. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | These include tau mislocalization to the cytoplasm, selective proteasomal degradation, or impaired nucleocytoplasmic transport dynamics. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Within the nucleus, AT8-phosphorylated tau may transiently interact with nucleolar components, such as fibrillarin, nucleolin, or RNA-binding proteins, thereby influencing ribosomal biogenesis and the maintenance of nucleolar integrity. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Disruption of these interactions, possibly coupled with altered phosphorylation turnover or stress-induced tau mislocalization, could compromise nucleolar homeostasis and contribute to neuronal vulnerability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Although AT8 is mainly detected within the nucleolus, its dynamic redistribution between nucleolar and nucleoplasmic compartments could indirectly influence chromatin organisation and transcriptional activity. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | This suggests that the role of nuclear AT8 phosphorylation is context-dependent and may reflect distinct cellular responses to stress and injury in proliferative versus terminally differentiated cells. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Together with the evidence of chromatin alterations, we observed progressive depletion of nucleolar fibrillarin and altered patterns of intranuclear histone H4 acetylation, consistent with transcriptional and chromatin reorganisation accompanying nuclear AT8 alterations. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, these results are correlative in nature and do not establish a direct mechanistic link between AT8 redistribution and nuclear remodelling. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While quantification of fibrillarin and H4Ac provides indirect measures of transcriptional activity and chromatin state, further studies involving co-localisation and functional assays will be required to elucidate the precise role of nuclear tau in regulating nucleolar function and transcription during ageing and neurodegeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Our results also suggest that nuclear tau phosphorylation at multiple epitopes—including AT8 (Ser202/Thr205), T181, S262, and S404 (PHF1)—may be associated with nucleolar activity, although AT8 shows the most consistent and dynamic changes. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In particular, the consistent nucleolar localisation of these phosphoepitopes observed both in neuroblastoma cells under different conditions (proliferative, differentiated, and transcriptionally inhibited) and in hippocampal CA1 neurons across ageing and Alzheimer’s disease stages points to a potential role of phosphorylated tau in supporting nucleolar structure and function, possibly contributing to the maintenance of ribosomal biogenesis and transcriptional homeostasis. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Notably, the unique decline of AT8 nucleolar localisation across life stages and Alzheimer’s disease progression—distinct from other epitopes—highlights a potentially critical role of this phosphorylation event in maintaining nucleolar homeostasis. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | This suggests that the loss of nuclear AT8 may represent a key event marking the shift from physiological to pathological tau function in post-mitotic neurons. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Moreover, the relatively stable nuclear presence of other phosphoepitopes may reflect less dynamic roles or reduced susceptibility to nuclear remodelling during ageing and neurodegeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Altogether, these findings reinforce the notion that phosphorylation of tau at the AT8 epitope is closely linked to neuronal cell cycle control mechanisms, and that its alteration may increase neuronal vulnerability and contribute to aberrant cell cycle re-entry observed in neurodegenerative conditions. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Our findings align with recent evidence suggesting that tau may exert a protective effect against neurodegeneration by modulating the neuronal cell cycle . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Taken together, these correlative results support a model in which nuclear tau plays a key role in maintaining neuronal homeostasis through regulation of chromatin state and suppression of aberrant cell cycle activity. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, functional validation in model systems remains essential to confirm these mechanisms. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Each experimental model used in this study has inherent limitations that should be considered when interpreting the results. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The SK-N-BE neuroblastoma cell line provides a tractable system to study differentiation-related nuclear tau changes but does not fully reproduce mature neuronal physiology, while post-mortem hippocampal tissue is subject to inter-individual variability and fixation effects. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, when used in combination, these complementary models provide convergent evidence supporting the robustness of our findings and allow cross-validation between controlled in vitro conditions and human pathological contexts. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The gradual loss of nuclear tau and the associated changes in the chromatin state, including fibrillarin reduction and histone H4 acetylation redistribution, provide new insights into the early molecular events in AD. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | These findings suggest that neuronal chromatin disorganisation may precede classical hallmarks of neurodegeneration, reinforcing the idea that the role of tau in the nucleus should be further investigated as a potential therapeutic target. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Future studies should test whether site-specific tau mutants (phospho-deficient or phospho-mimetic at S202/T205) affect nuclear localisation and neuronal stability in models like neuroblastoma cells. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Additionally, identifying biomarkers of nuclear tau depletion in accessible fluids could enable early AD detection. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | A critical aspect of Alzheimer’s disease pathogenesis is the identification of the initial molecular events that trigger neuronal degeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Our findings indicate that the disappearance of the AT8 epitope from the neuronal nucleus constitutes a key early event linked to neurodegeneration onset. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | This loss correlates with ectopic cell cycle reactivation, supporting the hypothesis that aberrant attempts to re-enter the cell cycle are a primary cause of neuronal death in AD. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The observed reduction in fibrillarin and changes in histone H4 acetylation patterns suggest nuclear remodelling events that may accompany the loss of nuclear tau, potentially affecting transcriptional stability and chromatin organisation. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Although our results are correlative in nature and based on a limited number of neuropathological samples, the integration of ex vivo human tissue with in vitro cellular models strengthens the reliability of our findings. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While each model presents specific limitations, their coordinated use offers a significant advantage: in vitro experiments enable controlled mechanistic observations, whereas human post-mortem analyses provide pathological validation. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The convergence of these approaches increases confidence in the observed relationship between nuclear tau depletion, chromatin remodelling, and neuronal vulnerability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Larger cohort studies will be essential to confirm these results and to further clarify the link between nuclear tau loss, chromatin remodelling, and neuronal vulnerability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Furthermore, our data indicate that tau phosphorylation at different sites may underlie distinct nuclear roles. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While multiple phosphoepitopes are stably retained in the nucleolus, the AT8 epitope (Ser202/Thr205) shows a progressive nuclear loss, emerging as a specific marker of chromatin vulnerability and neuronal stress in Alzheimer’s disease. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The identification of circulating biomarkers reflecting nuclear tau depletion could be a valuable tool for early detection of AD-related neurodegeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Therapeutic strategies aimed at preserving nuclear tau function may help maintain neuronal integrity and prevent disease progression. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In vivo studies and analyses of peripheral biofluids could further validate these findings and determine whether nuclear tau phosphorylation patterns, particularly AT8, may serve as accessible biomarkers of early neuronal vulnerability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Future research should focus on defining the molecular partners of nuclear tau and on investigating interventions that stabilise its nuclear functions in ageing neurons. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In addition, functional assays, such as transcriptional activity analyses, and transcriptomic or proteomic approaches could clarify the molecular pathways linking AT8 loss to cell cycle re-entry. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Although most therapeutic strategies currently focus on cytoplasmic tau, some may also influence nuclear tau, particularly those targeting tau phosphorylation, offering valuable translational perspectives for disease-modifying interventions. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Advanced cellular models and in vivo systems will be crucial to experimentally test these interventions and to assess their efficacy in preserving nuclear tau function and neuronal integrity. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Moreover, a deeper investigation of tau phosphorylation dynamics within the nucleolus could reveal a critical molecular crossroad linking chromatin remodelling and cell cycle reactivation in AD. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | By targeting the earliest neuronal dysfunction events, preventive strategies could be developed to mitigate Alzheimer’s disease progression before substantial neurodegeneration occurs. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Neuroblastoma is a highly lethal childhood tumour derived from differentiation-arrested neural crest cells. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Like all cancers, its growth is fuelled by metabolites obtained from either circulation or local biosynthesis. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Neuroblastomas depend on local polyamine biosynthesis, and the inhibitor difluoromethylornithine has shown clinical activity. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumour differentiation and profound survival gains in the Th-MYCN mouse model. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Specifically, an arginine- and proline-free diet decreases the amount of the polyamine precursor ornithine and enhances tumour polyamine depletion by difluoromethylornithine. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | This polyamine depletion causes ribosome stalling, unexpectedly specifically at codons with adenosine in the third position. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Thus, impaired translation of these codons, induced by combined dietary and pharmacological intervention, favours a pro-differentiation proteome. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | These results suggest that the genes of specific cellular programmes have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of paediatric cancers. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Hyperactive MYC signalling via amplification of the MYCN proto-oncogene is a hallmark of neuroblastoma and drives aggressive disease with poor outcomes. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | In the Th-MYCN genetically engineered mouse model, enforced MYCN expression in sympathoadrenal cells induces neuroblastomas. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | The rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC), is directly transcriptionally upregulated by MYCN and is often co-amplified. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Inhibition of ODC by difluoromethylornithine (DFMO) has recently been approved by the US Food and Drug Administration for treatment of children with high-risk neuroblastoma. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Combined treatment strategies to enhance DFMO activity are therefore of great interest. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | One potential such strategy is depletion of the ODC substrate ornithine. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Ornithine can be derived from arginine via a single enzymatic step catalysed by arginase, or from proline and glutamine via two or three steps that converge on the enzyme ornithine aminotransferase (OAT). |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | In early childhood, most ornithine comes from proline via OAT. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Since neuroblastomas arise in early childhood, they might similarly depend on OAT, which was recently implicated as a metabolic driver in pancreatic cancer through the provision of ornithine and thereby polyamines. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | We found that proline, whose catabolism can feed into ornithine via OAT, is strongly increased in MYCN-driven neuroblastoma. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | This was shown in three contexts: primary patient tumours exhibiting MYCN amplification (relative to unamplified tumours), xenografts induced from patient-derived neuroblastoma cell lines exhibiting high MYCN expression (relative to cell lines with low MYCN expression), and Th-MYCN genetically engineered mouse tumours (relative to normal organs of the mouse) (Fig. 1a,b, Extended Data Fig. 1 and Supplementary Table 1). |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | In the Th-MYCN model, proline content was also markedly higher in late tumours (those larger than 50 mm) compared with early tumours (Extended Data Fig. 1f). |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Gene-expression analysis indicated that proline transport and de novo biosynthesis is upregulated in MYCN-amplified patient tumours and cell lines (Extended Data Fig. 2), which is of interest as recent work has highlighted the necessity of reductive proline biosynthesis. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Levels of ornithine and other upstream precursors were not consistently higher in these cells. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Thus, we identified a large increase in proline in MYCN-driven neuroblastoma and propose proline as a candidate target for potential enhancement of neuroblastoma therapy. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Fig. 1MYCN-driven neuroblastoma tumours are characterized by high proline levels and a functionally disconnected proline and arginine metabolism that is dependent on uptake from circulation.a, Primary neuroblastoma tumour tissue was analysed using liquid chromatography–mass spectrometry-based metabolomics. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | b, Differential abundance of 303 metabolites. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Proline was the most significantly increased metabolite in MYCN-amplified primary human neuroblastoma relative to non-amplified tumours. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Dotted line marks the significance threshold, with P values corrected for a false discovery rate (FDR) of 0.05 (q < 0.05; n = 10). |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | c, In vivo stable isotope tracing identifies the circulating precursors of intratumoral metabolites. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Labelling is normalized to the serum for each infused [U-C] metabolite in Th-MYCN mice fed a chow diet. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Data are mean ± s.e.m. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Proline serum: n = 6; proline tumour: n = 4; glutamine serum: n = 9; glutamine tumour: n = 9; arginine serum: n = 8; arginine tumour: n = 8; ornithine serum: n = 7; ornithine tumour: n = 6. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | d, Direct circulating nutrient contributions to tumour tissue metabolite pools of proline, arginine and ornithine in Th-MYCN mice. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | The colour indicates the respective circulating nutrient source. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Contributions derived from [U-C]-labelled tracer infusions, derived from data shown in c. Data are mean ± s.e.m. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | e, Oral gavage of C-labelled nutrients shows the dietary contribution to circulating ornithine. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | The gavage feed introduces one-third of the daily intake of the respective amino acid in its [U-C] form, which is used to quantify its contribution to polyamine-related downstream metabolites over time. |
PMC12527938 | Reprogramming neuroblastoma by diet-enhanced polyamine depletion | Feeds in the Th-MYCN model are adapted to mouse weight. |
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