{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:57:20Z","timestamp":1792173440389,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T00:00:00Z","timestamp":1360108800000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Altered protein handling is thought to play a key role in the etiopathogenesis of Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>), as the disorder is characterized neuropathologically by the accumulation of intraneuronal protein aggregates (Lewy bodies and Lewy neurites). Attention has particularly focused on the \u03b1\u2010synuclein protein, as it is the principal component of Lewy pathology. Moreover, point mutations in the \u03b1\u2010synuclein gene cause rare familial forms of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. Importantly, duplication\/triplication of the wild type \u03b1\u2010synuclein gene also cause a form of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, indicating that increased levels of the normal \u03b1\u2010synuclein protein is sufficient to cause the disease. Further, single nucleotide polymorphisms in the \u03b1\u2010synuclein gene are associated with an increased risk of developing sporadic <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>. Recent evidence now suggests the possibility that \u03b1\u2010synuclein is a prion\u2010like protein and that <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> is a prion\u2010like disease. Within cells, \u03b1\u2010synuclein normally adopts an \u03b1\u2010helical conformation. However, under certain circumstances, the protein can undergo a profound conformational transition to a \u03b2\u2010sheet\u2013rich structure that polymerizes to form toxic oligomers and amyloid plaques. Recent autopsy studies of patients with advanced <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> who received transplantation of fetal nigral mesencephalic cells more than a decade earlier demonstrated that typical Lewy pathology had developed within grafted neurons. This suggests that \u03b1\u2010synuclein in an aberrantly folded, \u03b2\u2010sheet\u2013rich form had migrated from affected to unaffected neurons. Laboratory studies confirm that \u03b1\u2010synuclein can transfer from affected to unaffected nerve cells, where it appears that the misfolded protein can act as a template to promote misfolding of host \u03b1\u2010synuclein. This leads to the formation of larger aggregates, neuronal dysfunction, and neurodegeneration. Indeed, recent reports demonstrate that a single intracerebral inoculation of misfolded \u03b1\u2010synuclein can induce Lewy\u2010like pathology in cells that can spread from affected to unaffected regions and can induce neurodegeneration with motor disturbances in both transgenic and normal mice. Further, inoculates derived from the brains of elderly \u03b1\u2010synuclein\u2013overexpressing transgenic mice have now been shown to accelerate the disease process when injected into the brains of young transgenic animals. Collectively, these findings support the hypothesis that \u03b1\u2010synuclein is a prion\u2010like protein that can adopt a self\u2010propagating conformation that causes neurodegeneration. We propose that this mechanism plays an important role in the development of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> and provides novel targets for candidate neuroprotective therapies. \u00a9 2013 <jats:italic>Movement<\/jats:italic> Disorder Society<\/jats:p>","DOI":"10.1002\/mds.25373","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T20:19:30Z","timestamp":1360181970000},"page":"31-40","source":"Crossref","is-referenced-by-count":351,"title":["Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion\u2010Like Disorder?"],"prefix":"10.1002","volume":"28","author":[{"given":"C. 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