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Physiologically, \u03b1S may populate disordered monomeric, helically folded tetrameric, or membrane-bound oligomeric states. Pathologically, \u03b1S may assemble into toxic oligomers and subsequently fibrils, the prion-like transmission of which is implicated in a class of neurodegenerative disorders collectively termed \u03b1-synucleinopathies. Notably, \u03b1S does not adopt a single \u201camyloid fold\u201d, but rather exists as structurally distinct amyloid-like conformations referred to as \u201cstrains\u201d. The inoculation of animal models with different strains induces distinct pathologies, and emerging evidence suggests that the propagation of disease-specific strains underlies the differential pathologies observed in patients with different \u03b1-synucleinopathies. The characterization of \u03b1S strains has provided insight into the structural basis for the overlapping, yet distinct, symptoms of Parkinson\u2019s disease, multiple system atrophy, and dementia with Lewy bodies. In this review, we first explore the physiological and pathological differences between conformational states of \u03b1S. We then discuss recent studies on the influence of micro-environmental factors on \u03b1S species formation, propagation, and the resultant pathological characteristics. Lastly, we review how an understanding of \u03b1S conformational properties has been translated to emerging strain amplification technologies, which have provided further insight into the role of specific strains in distinct \u03b1-synucleinopathies, and show promise for the early diagnosis of disease.<\/jats:p>","DOI":"10.3390\/biom12070994","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["\u03b1-Synuclein Conformational Plasticity: Physiologic States, Pathologic Strains, and Biotechnological Applications"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-0272","authenticated-orcid":false,"given":"Amanda","family":"Li","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-556X","authenticated-orcid":false,"given":"Xiaobo","family":"Mao","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mao, X., Ou, M.T., Karuppagounder, S.S., Kam, T.-I., Yin, X., Xiong, Y., Ge, P., Umanah, G.E., Brahmachari, S., and Shin, J.-H. 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