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Clearing \u03b1-synOs while maintaining tissue homeostasis is a promising therapeutic strategy for PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We genetically engineered astrocytes with an anti-\u03b1-synO chimeric antigen receptor (CAR) consisting of a single-chain variable fragment targeting \u03b1-synOs and a truncated MerTK receptor, to direct their phagocytic activity against \u03b1-synOs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CAR-engineered astrocytes (CAR-A) showed significantly enhanced phagocytosis of \u03b1-synOs due to effective activation of Rac1, Cdc42 and RhoA and markedly decreased the release of pro-inflammatory cytokines by inhibiting the NF-\u03baB and cytokine receptor signaling pathways. Consistently, in situ CAR-A significantly ameliorated the motor and cognitive deficits of A53T mice by clearing \u03b1-synOs, creating a non-inflammatory microenvironment and restoring the viability of dopaminergic neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CAR-A-based strategy is an effective treatment for PD-like mouse model. This in situ CAR-A technology provides an innovative and feasible strategy to treat PD and other brain disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40035-025-00518-0","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T02:37:39Z","timestamp":1763606259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Attenuating \u03b1-synuclein pathology in mice with in situ engineered astrocytes"],"prefix":"10.1186","volume":"14","author":[{"given":"Xiao-yu","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-yu","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-han","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-yue","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-ru","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-lin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-4765","authenticated-orcid":false,"given":"Rui-tian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"issue":"6","key":"518_CR1","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s00401-017-1755-1","volume":"134","author":"N Bengoa-Vergniory","year":"2017","unstructured":"Bengoa-Vergniory N, Roberts RF, Wade-Martins R, Alegre-Abarrategui J. 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Cell Stem Cell. 2020;27(4):523\u201331.","journal-title":"Cell Stem Cell"}],"container-title":["Translational Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-025-00518-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40035-025-00518-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-025-00518-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T05:15:14Z","timestamp":1763615714000},"score":1,"resource":{"primary":{"URL":"https:\/\/translationalneurodegeneration.biomedcentral.com\/articles\/10.1186\/s40035-025-00518-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["518"],"URL":"https:\/\/doi.org\/10.1186\/s40035-025-00518-0","relation":{},"ISSN":["2047-9158"],"issn-type":[{"value":"2047-9158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"assertion":[{"value":"11 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were performed in accordance with the China Public Health Service Guide for the Care and Use of Laboratory Animals. Experiments and protocols involving mice were approved by the Institutional Animal Care and Use Committee of Tsinghua University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}