{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:47:13Z","timestamp":1782290833094,"version":"3.54.5"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo di Beneficenza Intesa San Paolo","award":["B\/2023\/0213"],"award-info":[{"award-number":["B\/2023\/0213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease and Alzheimer\u2019s disease are currently classified as a major global health burden, sharing a defining pathological hallmark represented by insoluble protein aggregates of \u03b1-synuclein (\u03b1-syn) and amyloid-\u03b2 (A\u03b2), respectively. A defining characteristic of all amyloids is a highly ordered, unbranched filamentous morphology, where individual \u03b2-strands align perpendicularly to the filament axis. Despite recent technological advances, direct observation of protein conformational changes and amyloid formation in biological samples remains a challenge as well as the quantification of pathological aggregates in liquid biopsies. This review critically recapitulates the major advances in the application of Raman spectroscopy (RS) and surface-enhanced Raman spectroscopy (SERS) in the investigation of pathological protein aggregates in neurological disorders, with a focus on \u03b1-syn and A\u03b2. We discuss both in vitro structural characterization and the applications to biological and clinical samples, outlining the main challenges for clinical translation, including the need for standardized protocols. Recent achievements in the use of RS and SERS on liquid biopsies and other clinical samples are paving the way for further implementation of Raman-based approaches for the diagnosis of neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms27125550","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Raman Spectroscopy for Probing Pathological Protein Aggregates: Potential and Perspectives for Advanced Diagnostic Applications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-5714","authenticated-orcid":false,"given":"Alice","family":"Gualerzi","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-7405","authenticated-orcid":false,"given":"Valentina","family":"Mangolini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-0508","authenticated-orcid":false,"given":"Luana","family":"Forleo","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8327-2732","authenticated-orcid":false,"given":"Chiara","family":"Cabrini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7592-0253","authenticated-orcid":false,"given":"Silvia","family":"Picciolini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-3661","authenticated-orcid":false,"given":"Marzia","family":"Bedoni","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","first-page":"2937","article-title":"The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need","volume":"16","author":"Wang","year":"2024","journal-title":"Aging Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/35081564","article-title":"Alpha-Synuclein and Neurodegenerative Diseases","volume":"2","author":"Goedert","year":"2001","journal-title":"Nat. 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