{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:11:21Z","timestamp":1792977081937,"version":"4.5.0"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The activation of microglia, which are the resident immune cells of the central nervous system (CNS), underpins the pathogenesis of neuroinflammatory and neurodegenerative diseases. Metabolic reprogramming has recently been recognized as a critical mechanism that regulates microglial activation because distinct activation phenotypes are tightly coupled to specific metabolic profiles that shape their functional and inflammatory responses. Accumulating evidence indicates that microglia produce itaconate through the tricarboxylic acid cycle, and itaconate and its derivatives play key antioxidant and anti-inflammatory roles. Mechanistically, itaconate has a major impact on the metabolic processes and functional state of microglia by blocking the NF-\u03baB signaling route, activating the Nrf2 signaling pathway, and inhibiting succinate dehydrogenase synthesis as well as NLRP3 inflammatory vesicle activation. Collectively, these actions confer significant protection against CNS disorders, including ischemic stroke, Alzheimer\u2019s disease, Parkinson\u2019s disease, and cerebral hemorrhage. Furthermore, structurally optimized itaconate derivatives exhibit enhanced pharmacokinetics and bioactivity. This review highlights the pivotal role of itaconate and its derivatives in microglial regulation, explores their therapeutic potential in neurological diseases, and outlines future research directions, with the aim of providing a theoretical foundation for novel metabolic interventions.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1726379","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:22:07Z","timestamp":1770355327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic control of neuroinflammation: focus on itaconate and its derivatives in CNS disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, the 960th Hospital of PLA (General Hospital of Jinan Military Command)","place":["Jinan, Shandong, China"]},{"name":"School of Clinical Medicine, Shandong First Medical 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