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This review integrates recent advances in EV proteomics to elucidate their roles in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and ischemic stroke. Across these conditions, EVs carry disease\u2010relevant proteins that reflect and influence key pathological processes such as synaptic dysfunction, neuroinflammation, blood\u2013brain barrier (BBB) disruption, and cell death. Proteomic profiling of brain\u2010 and biofluid\u2010derived EVs has uncovered specific biomarkers and signaling pathways, ranging from tau and \u03b1\u2010synuclein in AD and PD to mutant SOD1 in ALS and complement activation in stroke and TBI. Moreover, cell\u2010type\u2010specific EVs (e.g., from neurons, astrocytes, microglia, and stem cells) have been shown to exert either protective or deleterious effects, modulating apoptosis, axonal regeneration, and immune responses. Recent evidence highlights the translational potential of EVs as non\u2010invasive biomarkers and therapeutic vectors across multiple disorders. By mapping shared and divergent proteomic signatures in EVs, we review the mechanistic relevance and clinical utility of EVs in neurodegeneration and CNS injury.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70350-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70350","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:28:57Z","timestamp":1768404537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection"],"prefix":"10.1111","volume":"170","author":[{"given":"Berenice N.","family":"Bernal\u2010Vicente","sequence":"first","affiliation":[{"name":"Department of Molecular Neuropathology, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Ponce","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"R\u00edos\u2010Castro","sequence":"additional","affiliation":[{"name":"Genomics, Proteomics, and Metabolomics Unit National Laboratory of Experimental Services LaNSE, Cinvestav  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perla","family":"Moreno\u2010Castilla","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Resilience Centro de Investigaci\u00f3n Sobre el Envejecimiento, Cinvestav Sede Sur  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-1378","authenticated-orcid":false,"given":"Luis B.","family":"Tovar\u2010y\u2010Romo","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-018-1056-0"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205496"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.05.021"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15092173"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-025-02315-w"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-67171-6_5"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2317402121"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.425066"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/011570159X359837250611052037"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1469066719893492"},{"key":"e_1_2_14_12_1","doi-asserted-by":"crossref","unstructured":"Bezstarosti K. 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