{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:55:52Z","timestamp":1768557352982,"version":"3.49.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 106-2314-B-030-005, MOST 107-2314-B-030-009, MOST 108-2314-B-030-007, MOST 110-2314-B-030-008, and MOST 111-2314-B-030-007"],"award-info":[{"award-number":["MOST 106-2314-B-030-005, MOST 107-2314-B-030-009, MOST 108-2314-B-030-007, MOST 110-2314-B-030-008, and MOST 111-2314-B-030-007"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University","doi-asserted-by":"publisher","award":["A0206004, and A0209004"],"award-info":[{"award-number":["A0206004, and A0209004"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Abnormal accumulation of alpha-synuclein (\u03b1Syn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson\u2019s disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against \u03b1Syn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human \u03b1Syn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human \u03b1Syn. Upon the peptide injection, \u03b1Syn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening \u03b1Syn toxicity, this peptide vaccine caused an increase in the pathogenic species of \u03b1Syn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of \u03b1Syn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the \u03b1Syn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, \u03b1Syn accumulation, and neurodegeneration.<\/jats:p>","DOI":"10.1371\/journal.pone.0291927","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T17:29:59Z","timestamp":1695317399000},"page":"e0291927","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-5878","authenticated-orcid":true,"given":"Yu-Sung","family":"Chiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo-Jen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Jin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun-Lieh","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Syuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Ying","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuchun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5760-3617","authenticated-orcid":true,"given":"Hsi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Ching","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2439-1080","authenticated-orcid":true,"given":"Yun-Hsiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"issue":"6","key":"pone.0291927.ref001","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"5","author":"LM de Lau","year":"2006","journal-title":"Lancet Neurol"},{"issue":"6645","key":"pone.0291927.ref002","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"MG Spillantini","year":"1997","journal-title":"Nature"},{"issue":"6","key":"pone.0291927.ref003","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"MJ Armstrong","year":"2020","journal-title":"Jama"},{"issue":"17","key":"pone.0291927.ref004","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1523\/JNEUROSCI.20-17-06365.2000","article-title":"Subcellular localization of wild-type and Parkinson\u2019s disease-associated mutant alpha -synuclein in human and transgenic mouse brain","volume":"20","author":"PJ Kahle","year":"2000","journal-title":"J Neurosci"},{"issue":"4","key":"pone.0291927.ref005","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JPD-150642","article-title":"The Synaptic Function of \u03b1-Synuclein","volume":"5","author":"J. 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