ArticleCell death and differentiation2025
Age-related p53 SUMOylation accelerates senescence and tau pathology in Alzheimer's disease.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Ginkgolic acid targets HSPA8 to trigger ferroptosis in hepatocellular carcinomaPharmaceutical biology · 2026Article
- Metabolomics Analysis Revealed That SXZ Ameliorates Cognitive Impairment in Naturally Aged Rats by Promoting Glutathione Metabolism and Inhibiting the Ferroptosis Pathway.CNS neuroscience & therapeutics · 2026Article
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- PIAS1-mediated GSK3β SUMOylation exacerbates tauopathy and cognitive deficits in Alzheimer's disease models.Molecular psychiatry · 2026Article
- Regulatory effects of transcription factor PAX3 on human dental pulp stem cells.BMC oral health · 2026Article
- A p53-ΔNp73 signaling axis drives selective motor neuron degeneration in spinal muscular atrophy.bioRxiv : the preprint server for biology · 2026Article
- Tracheal aspirates of mechanically ventilated preterm infants possess cytopathic tau variants: a prospective exploratory study.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- SENP1 mitigates intervertebral disc degeneration: mechanisms involving suppression of pyroptosis and apoptosis in nucleus pulposus cells.Journal of orthopaedic surgery and research · 2026Article
- UBC9-mediated p53 SUMOylation drives tubular senescence and exacerbates acute kidney injury in mice.Acta pharmacologica Sinica · 2026Article
- A Landscape Analysis of Human SUMOylation.Molecular & cellular proteomics : MCP · 2026Article
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Targeting tubular NAT10 ameliorates the renal Tubulointerstitial Fibrosis in Obstructive and Folic Acid-Induced Nephropathy.International journal of biological sciences · 2026Article
- Epigenetic Changes in Alzheimer's Disease and Interventions for Therapy.Neuropsychiatric disease and treatment · 2026Review
- Blood-brain barrier dysfunction and peripheral immune activation in Alzheimer's disease: an inflammation-centered review.Frontiers in immunology · 2026Review
- Death-associated protein kinase 1-dependent SENP1 degradation increases tau SUMOylation and leads to cognitive dysfunction in a mouse model for tauopathy.Molecular neurodegeneration · 2025Article
- Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease.Aging and disease · 2025Review
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Authors and funding
9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain. Mechanistically, SUMOylation of p53 at K386 residue causes the dissociation of SET/p53 complex, thus releasing SET into the cytoplasm, SET further interacts with cytoplasmic PP2A and inhibits its activity, resulting in tau hyperphosphorylation in neurons. In addition, SUMOylation of p53 promotes the p53 Ser15 phosphorylation that mediates neuronal senescence. Notably, p53 SUMOylation contributes to synaptic damage and cognitive defects in AD model mice. We also demonstrate that the SUMOylation inhibiter, Ginkgolic acid, recovering several senescent phenotypes drove by p53 SUMOylation in primary neurons. These findings suggest a previously undiscovered etiopathogenic relationship between aging and AD that is linked to p53 SUMOylation and the potential of SUMOylated p53-based therapeutics for neurodegeneration such as Alzheimer's disease.
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