{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:02:53Z","timestamp":1790823773422,"version":"4.1.0"},"reference-count":186,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The risk of Parkinson\u2019s disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified \u03b1-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded \u03b1-synuclein may be a consequence of some genetic defect or\/and a failure of the protein clearance system. Importantly, \u03b1-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic\/or autophagic route in the final stages to execute cell death. The misfolded \u03b1-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and \u03b1-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, \u03b1-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson\u2019s disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder.<\/jats:p>","DOI":"10.3390\/cells10030598","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T06:22:32Z","timestamp":1615270952000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Nigral Coup in Parkinson\u2019s Disease by \u03b1-Synuclein and Its Associated Rebels"],"prefix":"10.3390","volume":"10","author":[{"given":"Jeswinder","family":"Sian-Hulsmann","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, University of Nairobi, P.O. Box 30197, 00100 Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Riederer","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy Margarete-Hoeppel-Platz 1, University Hospital Wuerzburg, 97080 Wuerzburg, Germany"},{"name":"Department Psychiatry, University of Southern Denmark Odense, J.B. Winslows Vey 18, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/mds.10305","article-title":"Systematic review of incidence studies of Parkinson\u2019s disease","volume":"18","author":"Twelves","year":"2003","journal-title":"Mov. 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