{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:15:45Z","timestamp":1789895745174,"version":"4.0.1"},"reference-count":269,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T00:00:00Z","timestamp":1546387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2014-0769"],"award-info":[{"award-number":["2014-0769"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["grant ID #10742 and grant ID #10742.01"],"award-info":[{"award-number":["grant ID #10742 and grant ID #10742.01"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007343","name":"University of Brescia","doi-asserted-by":"publisher","award":["BIOMANE"],"award-info":[{"award-number":["BIOMANE"]}],"id":[{"id":"10.13039\/501100007343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alpha-synuclein (\u03b1-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactants, \u03b1-syn is counted among the intrinsically disordered proteins (IDPs) family. As with many other IDPs, \u03b1-syn is considered a hub protein. This function is particularly relevant at synaptic sites, where \u03b1-syn is abundant and interacts with many partners, such as monoamine transporters, cytoskeletal components, lipid membranes, chaperones and synaptic vesicles (SV)-associated proteins. These protein\u2013protein and protein\u2013lipid membrane interactions are crucial for synaptic functional homeostasis, and alterations in \u03b1-syn can cause disruption of this complex network, and thus a failure of the synaptic machinery. Alterations of the synaptic environment or post-translational modification of \u03b1-syn can induce its misfolding, resulting in the formation of oligomers or fibrillary aggregates. These \u03b1-syn species are thought to play a pathological role in neurodegenerative disorders with \u03b1-syn deposits such as Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are referred to as synucleinopathies. Here, we aim at revising the complex and promiscuous role of \u03b1-syn at synaptic terminals in order to decipher whether \u03b1-syn molecular interactants may influence its conformational state, contributing to its aggregation, or whether they are just affected by it.<\/jats:p>","DOI":"10.3390\/ijms20010141","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T03:36:30Z","timestamp":1546486590000},"page":"141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-9412","authenticated-orcid":false,"given":"Francesca","family":"Longhena","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-3082","authenticated-orcid":false,"given":"Gaia","family":"Faustini","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Spillantini","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-1919","authenticated-orcid":false,"given":"Arianna","family":"Bellucci","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy"},{"name":"Laboratory for Preventive and Personalized Medicine, Department of molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbrc.2013.09.132","article-title":"Evolutionary aspects of the synuclein super-family and sub-families based on large-scale phylogenetic and group-discrimination analysis","volume":"441","author":"Yuan","year":"2013","journal-title":"Biochem. 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