PMCID string | Title string | Sentences string |
|---|---|---|
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Serum samples from three patients with previously reported Satoyoshi syndrome were analyzed in this study . |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | A brief summary of the three cases follows. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The first case was a 28-year-oldwoman from Albacete (Spain), who developed alopecia at 10 years of age. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Two years later, she began experiencing progressive, painful muscle spasms, followed by diarrhea with carbohydrate malabsorption, iron-deficiency anemia, weight loss, skeletal abnormalities, and amenorrhea. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | A definitive Satoyoshi syndrome diagnosis was not reached until the patient was 18 years old. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Treatment with prednisone (30 mg/day) and methotrexate (7.5 mg/week) was initiated, with dramatic improvement of muscle spasms, resolution of diarrhea, weight gain of 20 kg, and recovery of menstruation. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The second case was a 17-year-old girl from the Canary Islands (Spain), with a history of asthma and allergic rhinitis, presenting with alopecia universalis at 5 years of age. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | At 11 years of age, she exhibited painful, intermittent muscle spasms, significant growth retardation, diarrhea, and abdominal pain. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Her self-limiting muscle spasms, localized to the acral areas of her limbs, increased with physical activity and typically lasted several minutes. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The patient was diagnosed with Satoyoshi syndrome, and treatment with carbamazepine and otilonium bromide led to the disappearance of her muscle spasms and diarrhea. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The third case was a 38-year-old woman from Kiel (Germany). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | At 13 years of age, she began presenting muscle spasms, with jaw cramps being the most uncomfortable. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | She was treated with carbamazepine, prednisolone, and sexsteroids. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | After introducing low doses of methotrexate to the therapy, the patient recovered from muscle spasms, alopecia, and diarrhea. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | At 18 years of age, methotrexate and corticosteroid medication were tapered off, without relapse. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Initiation of sexsteroid treatment resulted in pubertal development and regular menstrual cycles. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | She has thus far experienced three pregnancies, all terminating in spontaneous abortions. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Two control groups were included as follows: (a) one consisting of 30 blood donors provided by the Albacete General University Hospital Blood Bank, and (b) a second group of patients with other neurological pathologies. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The patients included in this second category were a 58-year-old female with radiculopathy, a 41-year-old male with acute disseminated encephalomyelitis, a 55-year-old female with secondary progressive multiple sclerosis, a 73-year-old male with Parkinson’s disease, a 34-year-old female with encephalitis caused by human herpes virus type 6, and a 53-year-old male with demyelinating polyneuropathy. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Samples from these patients were provided by the Albacete General University Hospital Biobank. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The present study was compliant with the Declaration of Helsinki, and ethical approval was obtained prior to data and sample collection by the local Medicine Research Ethics Committee of the Albacete General University Hospital (Acta 04/2016 and Acta 10/2021). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | All participants provided written informed consent for this study. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | For the identification of autoantibodies in patient serum, we used whole brain homogenate (Biochain, Newark, CA, USA), lysates from SH-SY5Y (ATCC, Manassas, VA, USA) cells, and differentiated SH-SY5Y cells. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The brain homogenate was reconstituted according to the manufacturer’s instructions. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | SH-SY5Y cells were cultured in Dulbecco’s Modified Eagle Medium/Ham’s Nutrient Mixture F-12 (DMEM F-12) supplemented with 2 mM L-glutamine (Gibco, Grand Island, NY, USA), 100 U/mL penicillin and 100 U/mL streptomycin (penicillin–streptomycin; Gibco, Grand Island, NY, USA), and 10% (v/v) heat-inactivated fetal bovine serum (FBS; Gibco, Gaithersburg, MD, USA). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Cultures were grown in a humidified incubator at 37 °C under a 5% CO2 atmosphere. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | To induce differentiation, the SH-SY5Y cells were treated with 0.1% retinoic acid (Sigma-Aldrich, Saint Louis, MO, USA) for 5 days, with the medium changed every 2 days. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The culture medium of the SH-SY5Y cells was removed, and the cells were washed with ice-cold phosphate-buffered saline (PBS, 0.1 M phosphate, 0.15 M sodium chloride, pH 7.2) and lysed for 5 min in 300 μL of ice-cold lysis buffer (Pierce IP, Thermo Fisher Scientific, Rockford, IL, USA). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The cell lysates were centrifuged at 13,000× g for 10 min. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The supernatants were kept for Western blot analysis, and the pellets discarded. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Protein concentrations were determined spectrophotometrically using the Micro BCA Protein Reagent Kit (Thermo Fisher Scientific, Rockford, IL, USA). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | A total of 25 µg of protein from brain homogenate, SH-SY5Y lysate, and differentiated SH-SY5Y lysate were separated by electrophoresis on 8% SDS-PAGE gels for 30 min at 60V and 1.5–2 h at 100V. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Following electrophoresis, the proteins were transferred to nitrocellulose membranes (Immobilon; Millipore Corporation, Billerica, MA, USA) previously activated with transfer buffer [3 g of Base Trizma (Sigma-Aldrich, Saint Louis, MO, USA), 14.4 g of glycine (Sigma-Aldrich, Saint Louis, MO, USA), 200 mL of methanol, and 800 mL of milliQ water], in a Trans-Blot SD Semi-Dry Transfer Cell (Bio-Rad, Hercules, CA, USA) at a constant amperage of 20 mA for 1.5 h. Nonspecific protein binding was blocked using a blocking buffer, 10% w/v skimmed milk, and 0.1% Tween 20 (Sigma-Aldrich, Saint Louis, MO, USA) in PBS for 1 h at room temperature (RT). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The membranes were incubated overnight at 4 °C with patient serum samples or control serum samples, diluted 1:50 in a blocking buffer. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | After washing with PBS containing 0.1% v/v Tween 20, 5 times for 5 min, the membranes were incubated with an anti-human IgG secondary antibody (anti-human IgG (Fc specific)−peroxidase antibody produced in goat; Sigma-Aldrich, Saint Louis, MO, USA), diluted 1:1000 in blocking buffer at RT and washed again with PBS containing 0.1% v/v Tween 20, 5 times for 5 min. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Antibodies were detected using an enhanced chemiluminescence detection kit (GE Healthcare, Little Chalfont, Buckinghamshire, UK). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The images were acquired using atransilluminator (Luminescent Image Analyzer LAS-4000 mini, Fujifilm, Tokyo, Japan) with the image capture software LAS-4000 Image Reader (Fujifilm, Tokyo, Japan). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | In our first experiment, we assessed the autoimmune immunoreactivity of the serum from the Satoyoshi patients in brain homogenate and SH-SY5Y cell lysates. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | We observed a pattern of three bands between 70 and 100 kDa in both the brain homogenate and SH-SY5Y lysate samples. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | A higher intensity and definition of the bands was observed for the SH-SY5Y lysate (Figure 1a). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | An additional Western blot was performed to compare the SH-SY5Y lysate and the differentiated SH-SY5Y lysate. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The same band pattern was found for both lysates, with no differences in band intensity or definition (Figure 1b). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | In the second experiment using only SH-SY5Y lysate samples, we observed a common band pattern between 70 kDa and 100 kDa for the serum samples of the three Satoyoshi syndrome patients (Figure 2, E = case 1, F = case 2, G = case 3). |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | This band pattern was absent in the blood donors (Figure 2A–D) and the patients with other neurological conditions (Figure 2H–M), suggesting that this band pattern is specific to Satoyoshi syndrome. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | No other specific band pattern was found in the blood donors or the other neurological conditions group. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | We were able to identify a characteristic band pattern in our three patients with Satoyoshi syndrome, which was more visible using the SH-SY5Y cell lysate than the brain homogenate. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | No differences in band intensity or definition were found between the SH-SY5Y and differentiated SH-SY5Y cell lysates. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | This immunoreactive band pattern was absent in the serum of blood donors or patients with other neurological conditions. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | No specific band pattern was expected in either the donor group or in the patients with other neurological diseases. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Healthy individuals may present variations in their serum circulating antibodies, and the neurological patients presented different diseases from each other; therefore, a similar pattern among them could not be presumed. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The band pattern found in our study for our three Satoyoshi patients, between 70 and 100 kDa, is within the range of the bands described by Endo et al. (85 kDa) and Matsuura et al. (90 kDa), who employed a similar Western blot technique . |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | SH-SY5Y cells express a large number of proteins with molecular weights between 70 and 100 kDa, including those related to neurotransmission, neuronal growth, cell proliferation, cell adhesion, the cytoskeleton, and stress response, among others . |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Further analysis using additional techniques will be required to confirm the results and determine which specific proteins are targeted by the autoantibodies produced by patients with Satoyoshi syndrome. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The serum samples in this study were obtained at least 5 years after the onset of the disease, when the patients had already received treatment and no longer showed symptoms. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The persistence of these characteristic autoantibodies after treatment may allow a retrospective diagnosis. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The symptomatology of Satoyoshi syndrome takes years to fully develop, and the appearance of the different symptoms is heterogeneous across patients. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Up to now, diagnosis has been based on a typical clinical pattern. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | A future Western blot test could provide an early diagnosis when patients only present with alopecia or muscle spasms, for example. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Satoyoshi syndrome is a very rare disease; therefore, patients are very few and dispersed across the world, making it very difficult to obtain samples. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | However, samples from more patients are needed to prove the validity of the test. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | We hope that this preliminary evidence will encourage other professionals to contribute new samples and collaborate with our research. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Additionally, efforts should be made to identify the autoantibodies responsible for the immunoreactivity we found, as well as the target protein or proteins. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | In summary, we present a first preliminary approach suggesting that the Western blot technique could be used as a laboratory test to assist in Satoyoshi syndrome diagnosis. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | SH-SY5Y lysate is a suitable antigen alternative to human brain homogenate when using this technique. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | The advantages of SH-SY5Y lysate include improved band visualization, better reproducibility, and lower cost. |
PMC12610766 | Preliminary Evidence for a Western Blot Diagnosis of Satoyoshi Syndrome Using SH-SY5Y Neuroblastoma Cell Lysate as the Antigen Source | Additional studies involving more Satoyoshi syndrome patients are needed to validate our results. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Background/Objectives: Tau protein, a central player in Alzheimer’s disease (AD) pathology, is classically known for its role in microtubule stabilisation. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, accumulating evidence indicates that tau also localises to the neuronal nucleus, particularly the nucleolus, where it may regulate chromatin organisation and transcription. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In this study, we investigated whether different phosphorylation states of nuclear tau display age- and disease-dependent patterns, with a specific focus on the AT8 epitope (phospho-Ser202/Thr205). |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Methods: We analysed nuclear tau epitopes (Tau-1, AT8, PHF1, T181, and S262) by indirect immunofluorescence in SK-N-BE neuroblastoma cells under proliferative and retinoic acid-induced differentiated conditions and in post-mortem hippocampal CA1 neurons from foetal, young, aged, and AD brains. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Other functional markers (UBTF, Ki67, fibrillarin and acetylated histone H4) were used to assess nuclear organisation and function. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Results: Compared with the other epitopes, AT8 was unique in showing dynamic nuclear localisation: absent in proliferating cells but present after differentiation, abundant in young neurons, and significantly reduced in aged and AD samples. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Nuclear AT8 co-localised with Ki67, and its decline was associated with neuronal cell cycle re-entry and nucleolar disorganisation. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Conclusions: Among multiple nuclear tau epitopes, AT8 was the only one displaying age- and disease-related changes, and its reduction during ageing and AD correlates with nuclear stress, aberrant cell cycle activity, and neuronal vulnerability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Loss of nuclear AT8 may therefore represent an early marker of dysfunction in ageing and AD brains. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Neurodegenerative disorders represent a heterogeneous group of chronic and progressive conditions affecting the central nervous system (CNS), in which specific neuronal populations gradually lose their function and viability. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Among them, Alzheimer’s disease (AD) is the most prevalent and a major cause of dementia worldwide. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | A central pathological feature of AD is the abnormal accumulation of misfolded proteins, including β-amyloid (Aβ) and hyperphosphorylated tau, which contribute to synaptic dysfunction and neuronal loss. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Despite decades of research, the molecular mechanisms that initiate and sustain these processes remain incompletely understood . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Among the various hypotheses proposed in the literature regarding the etiopathogenesis of neurodegenerative disorders, substantial evidence accumulated over the last two decades has supported the “cell cycle hypothesis,” which suggests that aberrant re-entry of post-mitotic neurons into the cell cycle represents an early and critical event in AD. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | This dysregulation is closely linked to tau phosphorylation and nuclear tau depletion, leading to chromatin disorganisation and nucleolar dysfunction . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In AD, cell cycle alterations in vulnerable neurons appear to contribute to the accumulation of hyperphosphorylated tau, leading to the formation of neurofibrillary tangles (NFTs) and the simultaneous expression of cell cycle markers. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Specifically, tau phosphorylated at the AT8 epitope (Ser202/Thr205) localises to nuclear compartments such as the nucleolus and pericentromeric heterochromatin, where it may influence chromatin structure and transcriptional regulation . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In vitro and in vivo studies indicate that nuclear tau phosphorylation at epitopes including AT8, Tau-1, T181, and PHF1 correlates with neuronal differentiation states and nucleolar activity, suggesting a regulatory role in rDNA transcription and chromatin maintenance . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Dysregulation of this phosphorylation pattern has been associated with aberrant cell cycle re-entry and neuronal vulnerability in AD . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Several studies have specifically demonstrated the presence of Ki67 and cyclins in post-mitotic neurons of aged and AD brains , supporting the aberrant cell cycle re-entry hypothesis in neurodegeneration. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Neuronal cell cycle re-entry can be either “abortive,” where neurons die at the G1/S checkpoint, or “non-abortive,” in which post-mitotic neurons undergo DNA synthesis in the S phase but fail to complete mitosis, ultimately dying before the G2/M transition . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | It has been proposed that nuclear tau depletion is associated with chromatin instability at the nuclear lamina and nucleolus, along with dysfunctional nucleocytoplasmic reorganisation . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Intracellular NFTs and extracellular amyloid-β (Aβ) plaques are the main histopathological markers of AD, but their link to cognitive decline remains debated. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While senile plaques are weakly correlated with cognitive symptoms, hyperphosphorylated tau is more strongly associated with synaptic dysfunction and disease progression . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | The hippocampus, particularly CA1 neurons, is highly susceptible to tau pathology and neurodegeneration, making it a critical region for studying nuclear tau dynamics across ageing and disease progression . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | However, the precise mechanisms by which nuclear tau phosphorylation contributes to neuronal stability, nucleolar homeostasis, and cell cycle control remain poorly defined. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | While cytoplasmic NFTs are well-established hallmarks of AD and are closely associated with disease progression, recent findings indicate that nuclear tau localisation plays a critical role in the early stages of AD. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Specifically, nuclear tau has been detected in two primary locations: the nucleolus and pericentromeric heterochromatin . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In vitro studies have identified specific nuclear tau epitopes, such as Tau-1 (Pro189/Gly207) and AT8 (pSer202/Thr205), which may interact directly with DNA and/or RNA. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | These epitopes appear to be involved in early AD events, potentially linking nuclear tau to neuronal differentiation. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Notably, AT8 is considered a marker of neuronal differentiation, and its nucleolar localisation suggests an association with rDNA transcriptional repression . |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | In the present study, we focus on the nuclear functions of tau and its phosphorylation states, analysing neuroblastoma cells and human hippocampal neurons across different ages and AD stages. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Our aim is to elucidate how tau phosphorylation at specific nuclear epitopes correlates with nucleolar integrity, cell cycle re-entry, and neurodegenerative processes. |
PMC12650037 | Loss of AT8 Nuclear Tau as a Marker of Neuronal Ageing and Alzheimer’s Disease Progression | Understanding these nuclear tau dynamics could provide novel insights into early AD pathogenesis and highlight potential therapeutic targets. |
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