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Isolated autonomic dysfunction with predominant genitourinary dysfunction and orthostatic hypotension and REM sleep behavior disorder are common characteristics of a prodromal phase, which may occur years prior to motor-symptom onset. MSA is a unique synucleinopathy, in which alpha-synuclein (aSyn) accumulates and forms insoluble inclusions in the cytoplasm of oligodendrocytes, termed glial cytoplasmic inclusions (GCIs). The origin of, and precise mechanism by which aSyn accumulates in MSA are unknown, and, therefore, disease-modifying therapies to halt or slow the progression of MSA are currently unavailable. For these reasons, much focus in the field is concerned with deciphering the complex neuropathological mechanisms by which MSA begins and progresses through the course of the disease. This review focuses on the history, etiopathogenesis, neuropathology, as well as cell and animal models of MSA.<\/jats:p>","DOI":"10.1007\/s00702-021-02419-8","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T08:17:48Z","timestamp":1633594668000},"page":"1507-1527","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A historical review of multiple system atrophy with a critical appraisal of cellular and animal models"],"prefix":"10.1007","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4575-2380","authenticated-orcid":false,"given":"David J.","family":"Marmion","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3776-4162","authenticated-orcid":false,"given":"Wouter","family":"Peelaerts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-3294","authenticated-orcid":false,"given":"Jeffrey H.","family":"Kordower","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"2419_CR24","doi-asserted-by":"crossref","unstructured":"Adams R, van Bogaert L, van der Eecken H (1961) D\u00e9g\u00e9n\u00e9rescences nigro-stri\u00e9es et cerebello-nigro-stri\u00e9es; pp. 219\u2013232. 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