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Neurosci."],"abstract":"<jats:p>Poly(ADP-ribose) polymerase-1 (PARP-1) activation and \u03b1-synuclein (\u03b1-syn) aggregation are neuropathological hallmarks of Parkinson\u2019s disease. This review aims to summarize the extensive interplay between these two factors. PARP-1 induces conformational changes in \u03b1-syn through structural reorganization mediated by poly(ADP-ribose) (PAR). Stress conditions resulting from PARP-1 overactivation are involved in the post-transcriptional regulation of \u03b1-syn. Oxidative and nitrative stress triggered by PARP-1 overactivation participate in the post-translational modifications of \u03b1-syn. PAR also contributes to \u03b1-syn degradation pathways, thereby influencing \u03b1-syn levels. Conversely, \u03b1-syn indirectly promotes PARP-1\u2013dependent cell death via reactive oxygen species (ROS), suggesting a possible link through cell death pathways. These findings indicate that intracellular PARP-1, its metabolic products, and \u03b1-syn are closely associated, leading to dopaminergic neuronal vulnerability and potentially creating a vicious cycle of toxicity in PD pathology.<\/jats:p>","DOI":"10.3389\/fnins.2026.1774158","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:47:40Z","timestamp":1776059260000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction between Poly(ADP-ribose) polymerase-1 and \u03b1-synuclein pathology in Parkinson\u2019s disease"],"prefix":"10.3389","volume":"20","author":[{"given":"Peng","family":"Zhang","sequence":"first","affiliation":[{"name":"Guilin Medical University, Guilin","place":["Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Li","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin","place":["Guangxi, China"]},{"name":"Laboratory of Guangxi Clinical Research Center for Neurological Diseases, Guilin","place":["Guangxi, China"]},{"name":"Laboratory of Guangxi Zhuang Autonomous Region Clinical Translational Engineering Research Center for Digital Medicine, Guilin Medical University, Guilin","place":["Guangxi, China"]},{"name":"Laboratory of Big Data Intelligent Cloud Management for Neurological Diseases of Guangxi, Guilin","place":["Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin","place":["Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.1021\/acs.biochem.1c00478","article-title":"Lipid peroxidation products HNE and ONE promote and stabilize alpha-synuclein oligomers by chemical modifications.","volume":"60","author":"Andersen","year":"2021","journal-title":"Biochemistry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s40478-017-0452-6","article-title":"Mechanisms underlying extensive Ser129-phosphorylation in \u03b1-synuclein aggregates.","volume":"5","author":"Arawaka","year":"2017","journal-title":"Acta Neuropathol. 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