{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:20:30Z","timestamp":1793067630376,"version":"4.5.0"},"reference-count":83,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS100743"],"award-info":[{"award-number":["R01NS100743"]}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS100743"],"award-info":[{"award-number":["R01NS100743"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:p>\n                    Huntington\u2019s disease (HD) is a fatal neurodegenerative disease caused by an expanded polyglutamine (CAG) repeat in the N-terminal of the huntingtin protein (\n                    <jats:italic>HTT<\/jats:italic>\n                    ). Microglial activation and elevated proinflammatory cytokines are observed in HD brains, but the mechanisms regulating neuroinflammation and microglial activation are poorly understood. Metformin-mediated neuroprotection has been demonstrated in experimental models of neurodegeneration, including HD. We found that metformin inhibits mitochondrial DNA (mtDNA) release and subsequent neuroinflammation in the cortex and striatum of a mouse model of HD. Moreover, elevated proinflammatory cytokines and microglial activation are inhibited by metformin in HD transgenic mouse brains. Metformin reduced pathological microglial clusters and shifted toward a quiescent, homeostatic phenotype. Metformin improved aberrant immunometabolism in HD mouse brains and primary microglia. Mechanistically, we found that metformin regulates mitochondrial fission, reprograms deregulated metabolism in HD microglia, and controls microglial activation and inflammation in HD transgenic mice.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.201466","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:00:22Z","timestamp":1775145622000},"source":"Crossref","is-referenced-by-count":4,"title":["Metabolic reprogramming is critical to microglial activation in Huntington\u2019s disease"],"prefix":"10.1172","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-640X","authenticated-orcid":true,"given":"Abhishek","family":"Jauhari","sequence":"first","affiliation":[{"name":"Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam 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