ArticleScientific reports2019
Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
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Who cites it
163 citing papers in PubMed, 271 citations in OpenAlex.
- Article
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- Insulin resistance induced by pesticides is overcome by pancreatic islet adaptation in a mouse model of Parkinson's disease.Molecular metabolism · 2026Article
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- Deciphering novel genotypic biomarkers and functional alterations in double strand break repair pathways for Parkinson's disease.Scientific reports · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Parkinson's disease linked LRRK2 G2019S drives oxidative nuclear DNA damage and PARP1 hyperactive signaling.bioRxiv : the preprint server for biology · 2026Article
- Characteristics and mechanisms of cognitive impairment in Parkinson disease.Nature reviews. Neurology · 2026Review
- Interaction between Poly(ADP-ribose) polymerase-1 and α-synuclein pathology in Parkinson's disease.Frontiers in neuroscience · 2026Review
- Revisiting the alpha-synuclein paradox in melanoma-Parkinson's disease connection: more than a tale of two cell fates.Cellular and molecular life sciences : CMLS · 2025Review
- Lack of functional STING modulates immunity but does not protect dopaminergic neurons in the alpha-synuclein pre-formed fibrils Parkinson's disease mouse model.NPJ Parkinson's disease · 2025Article
- Nucleolar aggregation of key neuropathological proteins in the postmortem neurodegenerative brain.Acta neuropathologica · 2025Article
- Review
- Pathological α-synuclein perturbs nuclear integrity.Neurobiology of disease · 2025Article
- Determination of α-Synuclein Protein Interactions by μMap Photo-proximity Labeling.bioRxiv : the preprint server for biology · 2025Article
- Molecular recognition and structural plasticity in amyloid-nucleic acid complexes.Journal of structural biology · 2025Review
- Alpha-synuclein modulates the positioning of endolysosomes in melanoma cells.Human molecular genetics · 2025Article
- Establishment and Characterization of Behavioral Changes in the Nuclear Localization Human α-Synuclein Transgenic Mice.Diseases (Basel, Switzerland) · 2025Article
- Vimentin network dysregulation mediates neurite deficits inScience advances · 2025Article
- α-Synuclein Pathology in Synucleinopathies: Mechanisms, Biomarkers, and Therapeutic Challenges.International journal of molecular sciences · 2025Review
103 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
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Abstract
Alpha-synuclein is a presynaptic protein that forms abnormal cytoplasmic aggregates in Lewy body disorders. Although nuclear alpha-synuclein localization has been described, its function in the nucleus is not well understood. We demonstrate that alpha-synuclein modulates DNA repair. First, alpha-synuclein colocalizes with DNA damage response components within discrete foci in human cells and mouse brain. Removal of alpha-synuclein in human cells leads to increased DNA double-strand break (DSB) levels after bleomycin treatment and a reduced ability to repair these DSBs. Similarly, alpha-synuclein knock-out mice show increased neuronal DSBs that can be rescued by transgenic reintroduction of human alpha-synuclein. Alpha-synuclein binds double-stranded DNA and helps to facilitate the non-homologous end-joining reaction. Using a new, in vivo imaging approach that we developed, we find that serine-129-phosphorylated alpha-synuclein is rapidly recruited to DNA damage sites in living mouse cortex. We find that Lewy inclusion-containing neurons in both mouse model and human-derived patient tissue demonstrate increased DSB levels. Based on these data, we propose a model whereby cytoplasmic aggregation of alpha-synuclein reduces its nuclear levels, increases DSBs, and may contribute to programmed cell death via nuclear loss-of-function. This model could inform development of new treatments for Lewy body disorders by targeting alpha-synuclein-mediated DNA repair mechanisms.
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