{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:52:52Z","timestamp":1793303572647,"version":"4.5.0"},"reference-count":259,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001236","name":"Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nature Science Foundation of Hubei Province"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Brain-resident macrophages (BRMs), including microglia and border-associated macrophages (BAMs), are the core immune sentinels of the central nervous system (CNS). They originate from early embryonic yolk sac and fetal liver progenitors and maintain their population throughout life via self-renewal. During neurodevelopment, microglia maintain neural network homeostasis by phagocytosing apoptotic neural precursors and pruning synaptic connections. In adulthood, they rapidly respond to infection, injury, or protein aggregation, which can both promote repair and exacerbate neurotoxicity. BAMs, located in the meninges, perivascular spaces, and choroid plexus, play a key role in boundary homeostasis and peripheral immune signal surveillance. Recent studies reveal that BRMs exhibit dual roles in Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease (HD), multiple sclerosis (MS), as well as ischemic stroke, traumatic brain injury, and radiation-induced brain injury: they can protect neurons by clearing pathological proteins or cellular debris, but persistent inflammatory responses may drive neurodegeneration. In AD, microglia clear A\u03b2 plaques via triggering receptor expressed on myeloid cells 2 (TREM2) and ADGRG1 signaling, while BAMs regulate synaptic damage and cerebrovascular function through CD36-ROS and SPP1 pathways. In PD and HD, BRMs contribute to\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -synuclein- and mutant huntingtin-related inflammatory responses. In MS, BRMs modulate the pro\u2212\/anti-inflammatory balance through antigen presentation and cytokine signaling. Based on these mechanisms, therapeutic strategies targeting BRM functions are emerging, including NLRP3 inflammasome inhibitors, TREM2 agonists, and interventions promoting microglial neuroprotective phenotypes. Future approaches aiming to precisely modulate BRM plasticity and their interactions with the peripheral immune system may transform these immune sentinels from \u201cdisease drivers\u201d to \u201ctherapeutic allies,\u201d offering novel strategies for treating neurodegenerative diseases and brain injuries.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1726194","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:33Z","timestamp":1770614553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Reprogramming brain-resident macrophages: from disease drivers to therapeutic allies in neurological disorders"],"prefix":"10.3389","volume":"20","author":[{"given":"Peng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Jingzhou Hospital Affiliated to Yangtze University, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Chun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jingzhou Hospital Affiliated to Yangtze University, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medicine, Health Science Center, Yangtze University","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Ru","family":"Tang","sequence":"additional","affiliation":[{"name":"Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Institute, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1177\/18796397251330144","article-title":"Emerging roles of microglia and neuroinflammation in Huntington's disease: From pathophysiology to clinical trials","volume":"14","author":"Abedrabbo","year":"2025","journal-title":"J. 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