{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:45:10Z","timestamp":1785800710413,"version":"3.56.0"},"reference-count":288,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Anatomy"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Parkinson's disease is a multifactorial neurodegenerative disorder characterized by progressive dopaminergic neuronal loss in the substantia nigra pars compacta and widespread \u03b1\u2010synuclein pathology. Despite extensive research, the precise molecular mechanisms underlying neuronal death remain incompletely defined. Emerging evidence indicates that multiple forms of programmed cell death (PCD), including apoptosis, autophagy failure, ferroptosis, and necroptosis, contribute to dopaminergic degeneration in distinct but overlapping contexts. This review synthesizes current insights from both post\u2010mortem human studies and experimental models to delineate the biochemical and pathological signatures of these PCD pathways in Parkinson's disease. Post\u2010mortem findings demonstrate heterogeneous and often coexisting PCD markers, suggesting that different neuronal subsets within the substantia nigra pars compacta may follow distinct death programs depending on their metabolic profile, iron load, and inflammatory milieu. In contrast, experimental models reveal more discrete pathway\u2010specific activation patterns: apoptosis predominates in acute toxin paradigms, autophagy failure in genetic models, ferroptosis in iron\u2010overload and oxidative stress conditions, and necroptosis in inflammation\u2010augmented models. The apparent discrepancies between human and experimental evidence reflect differences in temporal resolution, pathogenic drivers, and\u00a0neuronal heterogeneity but together support a unified model of multifactorial, context\u2010dependent cell death. Finally, preclinical studies targeting these pathways, through caspase inhibition, autophagy enhancement, ferroptosis suppression, or necroptosis blockade, have provided proof\u2010of\u2010concept neuroprotection, although translation to clinical efficacy remains elusive. Understanding how these interconnected PCD pathways converge during Parkinson's disease progression is essential for developing multimodal therapeutic strategies that move beyond symptomatic relief toward accurate disease modification.<\/jats:p>","DOI":"10.1002\/ca.70057","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T20:35:58Z","timestamp":1765312558000},"page":"382-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Programmed Cell Death and Its Therapeutic Implications in Parkinson's Disease: A Review of Apoptosis, Autophagy, Ferroptosis, and Necroptosis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-5928","authenticated-orcid":false,"given":"Nour S.","family":"Erekat","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Jordan University of Science and Technology  Irbid Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00466"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32756"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010398"},{"key":"e_1_2_12_5_1","article-title":"Bach1 Derepression Is Neuroprotective in a Mouse Model of Parkinson's Disease","volume":"118","author":"Ahuja M.","year":"2021","journal-title":"Proceedings of the National Academy of Sciences of the United States of 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