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The role of \u03b2\u2010synuclein and \u03b3\u2010synuclein is less well understood in terms of physiological functions and potential contribution to human diseases. \u03b1\u2010synuclein has been investigated extensively in both cerebrospinal fluid (CSF) and blood as a potential biomarker for synucleinopathies. Recently, great attention has been also paid to \u03b2\u2010synuclein, whose CSF and blood levels seem to reflect synaptic damage and neurodegeneration independent of the presence of synucleinopathy. In this review, we aim to provide an overview on the pathophysiological roles of the synucleins. Because \u03b3\u2010synuclein has been poorly investigated in the field of synucleinopathy and its pathophysiological roles are far from being clear, we focus on the interactions between \u03b1\u2010synuclein and \u03b2\u2010synuclein in PD. We also discuss the role of \u03b1\u2010synuclein and \u03b2\u2010synuclein as potential biomarkers to improve the diagnostic characterization of synucleinopathies, thus highlighting their potential application in clinical trials for disease\u2010modifying therapies. \u00a9 2022 The Authors.\n                    <jats:italic>Movement Disorders<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n                  <\/jats:p>","DOI":"10.1002\/mds.28941","type":"journal-article","created":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T03:29:46Z","timestamp":1644031786000},"page":"669-683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Alpha and Beta Synucleins: From Pathophysiology to Clinical Application as Biomarkers"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-3620","authenticated-orcid":false,"given":"Lorenzo","family":"Barba","sequence":"first","affiliation":[{"name":"Section of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery University of Perugia  Perugia Italy"},{"name":"Department of Neurology University of Ulm  Ulm Germany"},{"name":"Department of Neurology Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle\/Saale Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Paolini Paoletti","sequence":"additional","affiliation":[{"name":"Section of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Section of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Section of Neurology, Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Halbgebauer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Oeckl","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm  Ulm Germany"},{"name":"German Center for Neurodegenerative Disorders Ulm (DZNE e. 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