{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:30:58Z","timestamp":1790767858078,"version":"4.1.0"},"reference-count":196,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PGC2018-096335-B-100"],"award-info":[{"award-number":["PGC2018-096335-B-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministry of Economy, Industry and Competitiveness","award":["BFU2015-64119-P"],"award-info":[{"award-number":["BFU2015-64119-P"]}]},{"name":"National Institute of Neurological Disorders and Stroke (NIH)","award":["R01NS102257"],"award-info":[{"award-number":["R01NS102257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b1-Synuclein amyloid aggregation is a defining molecular feature of Parkinson\u2019s disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer\u2019s disease. The process of \u03b1-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of \u03b1-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of \u03b1-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct \u03b1-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms21218043","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T11:43:06Z","timestamp":1603885386000},"page":"8043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Multiplicity of \u03b1-Synuclein Aggregated Species and Their Possible Roles in Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Pablo","family":"Gracia","sequence":"first","affiliation":[{"name":"Joint Unit BIFI-IQFR (CSIC), Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 D.","family":"Camino","sequence":"additional","affiliation":[{"name":"Joint Unit BIFI-IQFR (CSIC), Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Volpicelli-Daley","sequence":"additional","affiliation":[{"name":"Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-6687","authenticated-orcid":false,"given":"Nunilo","family":"Cremades","sequence":"additional","affiliation":[{"name":"Joint Unit BIFI-IQFR (CSIC), Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0968-0004(99)01445-0","article-title":"Protein misfolding, evolution and disease","volume":"24","author":"Dobson","year":"1999","journal-title":"Trends Biochem. 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