ArticleExperimental & molecular medicine2022
Senescence and impaired DNA damage responses in alpha-synucleinopathy models.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Rethinking Senescence Hallmarks in the Brain: Lessons From Peripheral Tissues and Challenges in Defining Neuronal Senescence.Aging cell · 2026Review
- Cellular Senescence in Neurodegeneration: From Cell Types to Therapeutic Opportunities.Biomedicines · 2026Review
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders.Molecular neurobiology · 2025Review
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- DNA Damage Response Regulation Alleviates Neuroinflammation in a Mouse Model of α-Synucleinopathy.Biomolecules · 2025Article
- A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.Science advances · 2025Article
- A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies.Molecular neurodegeneration · 2025Article
- Aging, cellular senescence and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- Advances in biomarkers and diagnostic significance of organ aging.Fundamental research · 2025Review
- Regulatory Network Inference of Induced Senescent Midbrain Cell Types Reveals Cell Type-Specific Senescence-Associated Transcriptional Regulators.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson's disease.Molecular neurodegeneration · 2024Article
- Review
- Article
- The role of cellular senescence in neurodegenerative diseases.Archives of toxicology · 2024Review
- Tau beyond Tangles: DNA Damage Response and Cytoskeletal Protein Crosstalk on Neurodegeneration.International journal of molecular sciences · 2024Review
- Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease.Communications biology · 2024Article
- Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein is a crucial element in the pathogenesis of Parkinson's disease (PD) and related neurological diseases. Although numerous studies have presented potential mechanisms underlying its pathogenesis, the understanding of α-synuclein-mediated neurodegeneration remains far from complete. Here, we show that overexpression of α-synuclein leads to impaired DNA repair and cellular senescence. Transcriptome analysis showed that α-synuclein overexpression led to cellular senescence with activation of the p53 pathway and DNA damage responses (DDRs). Chromatin immunoprecipitation analyses using p53 and γH2AX, chromosomal markers of DNA damage, revealed that these proteins bind to promoters and regulate the expression of DDR and cellular senescence genes. Cellular marker analyses confirmed cellular senescence and the accumulation of DNA double-strand breaks. The non-homologous end joining (NHEJ) DNA repair pathway was activated in α-synuclein-overexpressing cells. However, the expression of MRE11, a key component of the DSB repair system, was reduced, suggesting that the repair pathway induction was incomplete. Neuropathological examination of α-synuclein transgenic mice showed increased levels of phospho-α-synuclein and DNA double-strand breaks, as well as markers of cellular senescence, at an early, presymptomatic stage. These results suggest that the accumulation of DNA double-strand breaks (DSBs) and cellular senescence are intermediaries of α-synuclein-induced pathogenesis in PD.
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