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We also show that manipulation of two \u03b2-arrestins produces contrary effects on the anti-inflammatory states and neuroprotective action of microglia induced by IL-4 in vivo and in vitro. We further find that the functional antagonism of two \u03b2-arrestins is mediated through sequential activation of sterile alpha motif domain containing 4 (Samd4), mammalian target of rapamycin (mTOR), and mitochondrial oxidative phosphorylation (OXPHOS). Collectively, these data reveal opposing functions of two closely related \u03b2-arrestins in regulating the IL-4\u2013induced microglia reactivity via the Samd4\/mTOR\/OXPHOS axis in PD mouse models and provide important insights into the pathogenesis and therapeutics of PD.<\/jats:p>","DOI":"10.1126\/sciadv.adn4845","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T18:27:22Z","timestamp":1724264842000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["Antagonism of \u03b2-arrestins in IL-4\u2013driven microglia reactivity via the Samd4\/mTOR\/OXPHOS axis in Parkinson\u2019s disease"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1422-9121","authenticated-orcid":true,"given":"Jiaqi","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical 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