{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:55:03Z","timestamp":1790776503212,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The aggregation of proteins into amyloid fibers is linked to more than forty still incurable cellular and neurodegenerative diseases such as Parkinson\u2019s disease (PD), multiple system atrophy, Alzheimer\u2019s disease and type 2 diabetes, among others. The process of amyloid formation is a main feature of cell degeneration and disease pathogenesis. Despite being methodologically challenging, a complete understanding of the molecular mechanism of aggregation, especially in the early stages, is essential to find new biological targets for innovative therapies. Here, we reviewed selected examples on \u03b1-syn showing how complementary approaches, which employ different biophysical techniques and models, can better deal with a comprehensive study of amyloid aggregation. In addition to the monomer aggregation and conformational transition hypothesis, we reported new emerging theories regarding the self-aggregation of \u03b1-syn, such as the alpha-helix rich tetramer hypothesis, whose destabilization induce monomer aggregation; and the liquid-liquid phase separation hypothesis, which considers a phase separation of \u03b1-syn into liquid droplets as a primary event towards the evolution to aggregates. The final aim of this review is to show how multimodal methodologies provide a complete portrait of \u03b1-syn oligomerization and can be successfully extended to other protein aggregation diseases.<\/jats:p>","DOI":"10.3390\/molecules27010088","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:06:54Z","timestamp":1640567214000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Implementing Complementary Approaches to Shape the Mechanism of \u03b1-Synuclein Oligomerization as a Model of Amyloid Aggregation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8847-9604","authenticated-orcid":false,"given":"Marco","family":"Giamp\u00e0","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres Gate 9, 7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-5775","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Amundarain","sequence":"additional","affiliation":[{"name":"Instituto de F\u00edsica del Sur (IFISUR), Departamento de F\u00edsica, Universidad Nacional del Sur (UNS), CONICET, Av. L. N. Alem 1253, Bah\u00eda Blanca B8000CPB, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-7410","authenticated-orcid":false,"given":"Maria Georgina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-5676","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Tonali","sequence":"additional","affiliation":[{"name":"BioCIS, CNRS, Facult\u00e9 de Pharmacie, Universit\u00e9 Paris-Saclay, 92290 Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-1880","authenticated-orcid":false,"given":"Veronica I.","family":"Dodero","sequence":"additional","affiliation":[{"name":"Organic and Bioorganic Chemistry, Chemistry Department, Bielefeld University, Universit\u00e4tstr. 25, 33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","article-title":"Protein Misfolding, Aggregation, and Conformational Strains in Neurodegenerative Diseases","volume":"21","author":"Soto","year":"2018","journal-title":"Nat. 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