{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:12:23Z","timestamp":1793401943442,"version":"4.5.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005667","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Considerable attention has been recently devoted to the involvement of immune cells in the central nervous system (CNS) during infections with neurotropic viruses, such as SARS-CoV-2, HIV-1, and ZIKV. These viruses are capable of infecting astrocytes and microglia, the main glial cells in the CNS, responsible for regulating neuronal activity. Here, we discuss how viral infections lead to metabolic reprogramming toward aerobic glycolysis in these cells, enhancing pro-inflammatory pathways, such as inflammasome activation, resulting in the secretion of inflammatory cytokines that favor the development of neuroinflammation. In this mini review, we discuss the pivotal interplay between metabolism and immunity towards viral pathogenesis in the CNS, pointing out the relevance of therapeutic strategies targeting both metabolic and immunological pathways to enhance antiviral and neuroprotective responses.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1686774","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:17:33Z","timestamp":1766121453000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Viral reprogramming of glial metabolism as a driver of neuroinflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Tamara","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Salles","family":"Beltr\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helo\u00edsa","family":"Girardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aguinaldo R.","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20928","article-title":"Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury","volume":"58","author":"Lehnardt","year":"2010","journal-title":"Glia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvw009","article-title":"Microglia in central nervous system repair after injury","volume":"159","author":"Jin","year":"2016","journal-title":"J Biochem"},{"key":"B3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl Neurodegener"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.04.001","article-title":"The role of astrocyte dysfunction in parkinson\u2019s disease pathogenesis","volume":"40","author":"Booth","year":"2017","journal-title":"Trends Neurosci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1217451","article-title":"Astrocyte metabolism and signaling pathways in the CNS","volume":"17","author":"Zhang","year":"2023","journal-title":"Front Neurosci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/imr.12858","article-title":"Immunometabolism: From basic mechanisms to translation","volume":"295","author":"Makowski","year":"2020","journal-title":"Immunol Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001356","article-title":"Neuroinflammation and immunometabolism in neurodegenerative diseases","volume":"38","author":"Lonkar","year":"2025","journal-title":"Curr Opin Neurol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16259","article-title":"Fundamental Neurochemistry Review: Lipids across microglial states","volume":"169","author":"Traetta","year":"2025","journal-title":"J Neurochem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00652-3","article-title":"Innate metabolic responses against viral infections","volume":"4","author":"Palmer","year":"2022","journal-title":"Nat Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1578202","article-title":"Metabolic reprogramming in viral infections: the interplay of glucose metabolism and immune responses","volume":"16","author":"Darweesh","year":"2025","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.03.006","article-title":"Molecular and metabolic heterogeneity of astrocytes and microglia","volume":"35","author":"Hasel","year":"2023","journal-title":"Cell Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.128.3322.450","article-title":"Oxidative phosphorylation","volume":"128","author":"Lehninger","year":"1958","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"104331","DOI":"10.1016\/j.neuint.2018.11.006","article-title":"Microglia metabolism in health and disease","volume":"130","author":"Borst","year":"2019","journal-title":"Neurochem Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5745","article-title":"Redox control of microglial function: molecular mechanisms and functional significance","volume":"21","author":"Rojo","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00493","article-title":"Metabolic reprograming of microglia in the regulation of the innate inflammatory response","volume":"11","author":"Lauro","year":"2020","journal-title":"Front Immunol"},{"key":"B16","article-title":"Exercise facilitates the M1-to-M2 polarization of microglia by enhancing autophagy via the BDNF\/AKT\/mTOR pathway in neuropathic pain","volume":"25","author":"Bai","year":"2022","journal-title":"Pain Physician"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0807","article-title":"Glycometabolic reprogramming of microglia in neurodegenerative diseases: insights from neuroinflammation","volume":"15","author":"Huang","year":"2024","journal-title":"Aging Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.742065","article-title":"Microglia in neuroinflammation and neurodegeneration: from understanding to therapy","volume":"15","author":"Muzio","year":"2021","journal-title":"Front Neurosci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01114","article-title":"Astrocytes: role and functions in brain pathologies","volume":"10","author":"Siracusa","year":"2019","journal-title":"Front Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25168922","article-title":"Metabolic reprogramming of astrocytes in pathological conditions: implications for neurodegenerative diseases","volume":"25","author":"Cal\u00ec","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.tem.2022.03.001","article-title":"Metabolic changes favor the activity and heterogeneity of reactive astrocytes","volume":"33","author":"Xiong","year":"2022","journal-title":"Trends Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41582-023-00822-1","article-title":"Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration","volume":"19","author":"Patani","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J Neuroinflammation"},{"key":"B24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","article-title":"Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders","volume":"24","author":"Brandebura","year":"2023","journal-title":"Nat Rev Neurosci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029","article-title":"Neuro-toxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02405-x","article-title":"The long non-coding RNA NEAT1\/miR-224-5p\/IL-33 axis modulates macrophage M2a polarization and A1 astrocyte activation","volume":"58","author":"Liu","year":"2021","journal-title":"Mol Neurobiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40478-023-01526-9","article-title":"Roles of neuropathology-associated reactive astrocytes: a systematic review","volume":"11","author":"Lawrence","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03761-6","article-title":"Molecular mechanisms associated with neurodegeneration of neurotropic viral infection","volume":"61","author":"Wongchitrat","year":"2024","journal-title":"Mol Neurobiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e0109122","DOI":"10.1128\/spectrum.01091-22","article-title":"SARS-coV-2 infection of microglia elicits proinflammatory activation and apoptotic cell death","volume":"10","author":"Jeong","year":"2022","journal-title":"Microbiol Spectr"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e2200960119","DOI":"10.1073\/pnas.2200960119","article-title":"Morphological, cellular, and molecular basis of brain infection in COVID-19 patients","volume":"119","author":"Crunfli","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e0230822","DOI":"10.1128\/mbio.02308-22","article-title":"Neuropilin-1 mediates SARS-coV-2 infection of astrocytes in brain organoids, inducing inflammation leading to dysfunction and death of neurons","volume":"13","author":"Kong","year":"2022","journal-title":"mBio"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-021-10015-6","article-title":"Mitochondrial dynamics in SARS-COV2 spike protein treated human microglia: implications for neuro-COVID","volume":"16","author":"Clough","year":"2021","journal-title":"J Neuroimmune Pharmacol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/14787210.2018.1466702","article-title":"Neurological complications of Zika virus infection","volume":"16","author":"Carod-Artal","year":"2018","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00437-0","article-title":"Aberrant NAD+ metabolism underlies Zika virus-induced microcephaly","volume":"3","author":"Pang","year":"2021","journal-title":"Nat Metab"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e0208543","DOI":"10.1371\/journal.pone.0208543","article-title":"Toll-like receptor 3 regulates Zika virus infection and associated host inflammatory response in primary human astrocytes","volume":"14","author":"Ojha","year":"2019","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw878","article-title":"Zika virus infects human fetal brain microglia and induces inflammation","volume":"64","author":"Lum","year":"2017","journal-title":"Clin Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"110118","DOI":"10.1016\/j.celrep.2021.110118","article-title":"Dysregulated metabolism underpins Zika-virus-infection-associated impairment in fetal development","volume":"37","author":"Yau","year":"2021","journal-title":"Cell Rep"},{"key":"B38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.14336\/AD.2019.0323","article-title":"Long-term HIV-1 tat expression in the brain led to neurobehavioral, pathological, and epigenetic changes reminiscent of accelerated aging","volume":"11","author":"Zhao","year":"2020","journal-title":"Aging Dis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/s12035-020-02131-w","article-title":"HIV-tat and cocaine impact brain energy metabolism: redox modification and mitochondrial biogenesis influence NRF transcription-mediated neurodegeneration","volume":"58","author":"Sivalingam","year":"2021","journal-title":"Mol Neurobiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300152","article-title":"HIV-1 tat upregulates TREM1 expression in human microglia","volume":"11","author":"Campbell","year":"2023","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577728","article-title":"The microglial NLRP3 inflammasome is involved in human SARS-CoV-2 cerebral pathogenicity: A report of three post-mortem cases","volume":"361","author":"Cama","year":"2021","journal-title":"J Neuroimmuno"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01871-z","article-title":"Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19","volume":"28","author":"Fekete","year":"2025","journal-title":"Nat Neurosci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.3390\/ijms23095150","article-title":"Shared inflammatory pathology of stroke and COVID-19","volume":"23","author":"S\u00e1nchez","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.01.158","article-title":"Zika virus induces inflammasome activation in the glial cell line U87-MG","volume":"492","author":"Tricarico","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e40","DOI":"10.4110\/in.2019.19.e40","article-title":"Zika virus impairs host NLRP3-mediated inflammasome activation in an NS3-dependent manner","volume":"19","author":"Gim","year":"2019","journal-title":"Immune Netw"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70061","article-title":"Caspase-1\/11 controls Zika virus replication in astrocytes by inhibiting glycolytic metabolism","volume":"292","author":"de Farias","year":"2025","journal-title":"FEBS J"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-11-35","article-title":"Rapid inflammasome activation in microglia contributes to brain disease in HIV\/AIDS","volume":"11","author":"Walsh","year":"2014","journal-title":"Retrovirology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00600.2023","article-title":"Cenicriviroc prevents dysregulation of astrocyte\/endothelial cross talk induced by ischemia and HIV-1 via inhibiting the NLRP3 inflammasome and pyroptosis","volume":"326","author":"Fattakhov","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e0237022","DOI":"10.1128\/mbio.02370-22","article-title":"Herpes simplex virus 1-induced ferroptosis contributes to viral encephalitis","volume":"14","author":"Xu","year":"2023","journal-title":"ASM J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1002250","DOI":"10.1371\/journal.ppat.1002250","article-title":"HSV infection induces production of ROS, which potentiate signaling from pattern recognition receptors: role for S-glutathionylation of TRAF3 and 6","volume":"7","author":"Gonzalez-Dosal","year":"2011","journal-title":"PloS Pathog"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-35","article-title":"Research Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2","volume":"7","author":"Schachtele","year":"2010","journal-title":"J Neuroinflammation"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/v13122364","article-title":"Innate immune signaling and role of glial cells in herpes simplex virus- and rabies virus-induced encephalitis","volume":"13","author":"Feige","year":"2021","journal-title":"Viruses"},{"key":"B53","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12974-024-03166-9","article-title":"Herpes simplex virus 1 accelerates the progression of Alzheimer\u2019s disease by modulating microglial phagocytosis and activating NLRP3 pathway","volume":"21","author":"Wang","year":"2024","journal-title":"J Neuroinflamm"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00844","article-title":"The proteome and secretome of cortical brain cells infected with herpes simplex virus","volume":"11","author":"Hensel","year":"2020","journal-title":"Front Neurol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.816098","article-title":"Epstein-barr virus and neurological diseases","volume":"8","author":"Zhang","year":"2022","journal-title":"Front Mol Biosci"},{"key":"B56","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41392-020-00376-4","article-title":"Targeting the signaling in Epstein\u2013Barr virus-associated diseases: mechanism, regulation, and clinical study","volume":"6","author":"Cao","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1557483","article-title":"Exploring the role of EBV in multiple sclerosis pathogenesis through EBV interactome","volume":"16","author":"Ballerini","year":"2025","journal-title":"Front Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s12985-025-02874-9","article-title":"Brain-specific expression of cytomegalovirus immediate early protein 1 disrupts neurodevelopment in mice by inducing neuroinflammation and altering astrocytic metabolism","volume":"22","author":"Yu","year":"2025","journal-title":"Virol J"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e20201503","DOI":"10.1084\/jem.20201503","article-title":"NK\/ILC1 cells mediate neuroinflammation and brain pathology following congenital CMV infection","volume":"218","author":"Kvestak","year":"2021","journal-title":"J Exp Med"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e0194221","DOI":"10.1128\/JVI.01942-21","article-title":"Comprehensive analysis of protein acetylation and glucose metabolism in mouse brains infected with rabies virus","volume":"96","author":"Pei","year":"2022","journal-title":"J Virol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/v16111774","article-title":"The immune escape strategy of rabies virus and its pathogenicity mechanisms","volume":"16","author":"Kiflu","year":"2024","journal-title":"Viruses"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e0130624","DOI":"10.1371\/journal.pone.0130624","article-title":"NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes","volume":"10","author":"Gustin","year":"2015","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.03.011","article-title":"AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice","volume":"87","author":"Kim","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/s1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02528-y","article-title":"Pyroptosis in Alzheimer\u2019s disease: cell type-specific activation in microglia, astrocytes and neurons","volume":"145","author":"Moonen","year":"2023","journal-title":"Acta Neuropathol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-023-08753-2","article-title":"Inflammasome activation mediates apoptotic and pyroptotic death in astrocytes under ischemic conditions","volume":"25","author":"Wong","year":"2023","journal-title":"NeuroMol Med"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.02.035","article-title":"ATP-P2X7 signaling mediates brain pathology while contributing to viral control in perinatal Zika virus infection","volume":"118","author":"Leite-Aguiar","year":"2024","journal-title":"Brain Behav Immun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106625","article-title":"The NLRP3 inflammasome in depression: Potential mechanisms and therapies","volume":"187","author":"Xia","year":"2023","journal-title":"Pharmacol Res"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607769113","article-title":"GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes","volume":"113","author":"Aglietti","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"B71","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s00401-022-02466-9","article-title":"Increased pyroptosis activation in white matter microglia is associated with neuronal loss in ALS motor cortex","volume":"144","author":"Van Schoor","year":"2022","journal-title":"Acta Neuropathol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00011-017-1095-6","article-title":"Nrf2\/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion","volume":"67","author":"Xu","year":"2018","journal-title":"Inflam Res"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2025.149560","article-title":"Galectin-3 activates microglia and promotes neurological impairment via NLRP3\/pyroptosis pathway following traumatic brain injury","volume":"1855","author":"Sun","year":"2025","journal-title":"Brain Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.expneurol.2024.114777","article-title":"Galectin-3 induces microglial A1-like reactive phenotype through TLR4-NF-\u03baB\/NLRP3 signaling","volume":"19","author":"Li","year":"2022","journal-title":"J Neuroinflammation"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04169-6","article-title":"Aberrant enhanced NLRP3 inflammasomes and cell pyroptosis in brains of prion-infected rodent models are largely associated with proliferative astrocytes","volume":"61","author":"Zhou","year":"2024","journal-title":"Mol Neurobiol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.155563","article-title":"The AIM2 inflammasome is activated in astrocytes during the late phase of EAE","volume":"7","author":"Barclay","year":"2022","journal-title":"JCI Insight"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.04.007","article-title":"Inflammasome signaling in astrocytes modulates hippocampal plasticity","volume":"58","author":"Zengeler","year":"2025","journal-title":"Immunity"},{"key":"B78","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00011-024-01984-4","article-title":"The role of NLRP3 inflammasome-mediated pyroptosis in astrocytes during hyperoxia-induced brain injury","volume":"74","author":"Liu","year":"2025","journal-title":"Inflammation Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2183026","article-title":"ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia\/reperfusion injury","volume":"2016","author":"Minutoli","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00771-8","article-title":"The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice","volume":"24","author":"Rhea","year":"2021","journal-title":"Nat Neurosci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00495-9","article-title":"SARS-CoV-2 spike protein interacts with and activates TLR41","volume":"31","author":"Zhao","year":"2021","journal-title":"Cell Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41586-024-07167-9","article-title":"Mitochondrial complex I activity in microglia sustains neuroinflammation","volume":"628","author":"Peruzzotti-Jametti","year":"2024","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/nri2725","article-title":"NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production","volume":"10","author":"Tschopp","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/s41590-022-01185-3","article-title":"Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation","volume":"23","author":"Billingham","year":"2022","journal-title":"Nat Immunol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"4034","DOI":"10.1038\/s41598-019-40619-1","article-title":"The NLRP3 inflammasome modulates glycolysis by increasing PFKFB3 in an IL-1\u03b2-dependent manner in macrophages","volume":"9","author":"Finucane","year":"2019","journal-title":"Sci Rep"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13280","article-title":"PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation","volume":"7","author":"Xie","year":"2016","journal-title":"Nat Commun"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8855585","article-title":"Increased succinate accumulation induces ROS generation in in vivo ischemia\/reperfusion-affected rat kidney mitochondria","volume":"2020","author":"Kamarauskaite","year":"2020","journal-title":"BioMed Res Int"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.01.007","article-title":"NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer\u2019s disease progression","volume":"58","author":"McManus","year":"2025","journal-title":"Immunity"},{"key":"B90","doi-asserted-by":"publisher","first-page":"102032","DOI":"10.1016\/j.arr.2023.102032","article-title":"Metabolic reprogramming and polarization of microglia in Parkinson\u2019s disease: Role of inflammasome and iron","volume":"90","author":"Yu","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.16.176990","article-title":"Defining the syndrome associated with congenital Zika virus infection","volume":"94","author":"Costello","year":"2016","journal-title":"Bull World Health Organ"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112189","article-title":"SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice","volume":"42","author":"Fontes-Dantas","year":"2023","journal-title":"Cell Rep"},{"key":"B93","doi-asserted-by":"publisher","first-page":"e20201707","DOI":"10.1084\/jem.20201707","article-title":"Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients","volume":"218","author":"Rodrigues","year":"2020","journal-title":"J Exp Med"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad037","article-title":"Casp4\/11 contributes to Nlrp3 activation and covid-19 exacerbation","volume":"227","author":"Rodrigues","year":"2023","journal-title":"J Infect Dis"},{"key":"B95","doi-asserted-by":"publisher","first-page":"e1012222","DOI":"10.1371\/journal.ppat.1012222","article-title":"Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19","volume":"20","author":"de S\u00e1","year":"2024","journal-title":"PloS Pathog"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104969","article-title":"Inflammasomes as biomarkers and therapeutic targets in traumatic brain injury and related-neurodegenerative diseases: A comprehensive overview","volume":"144","author":"Kattan","year":"2023","journal-title":"Neurosci Biobehav Rev"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01831-0","article-title":"SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein","volume":"28","author":"Albornoz","year":"2023","journal-title":"Mol Psychiatry"},{"key":"B98","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41392-022-01291-6","article-title":"COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy","volume":"8","author":"Zhang","year":"2023","journal-title":"Transduct Target Ther"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1368465","article-title":"Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1\/OPN and inflammasome pathway signaling","volume":"15","author":"Argandona Lopez","year":"2024","journal-title":"Front Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-023-01444-3","article-title":"Microglial inflammatory responses to SARS-coV-2 infection: A comprehensive review","volume":"44","author":"Dey","year":"2023","journal-title":"Cell Mol Neurobiol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011226118","article-title":"NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer\u2019s disease via cGAS-STING","volume":"118","author":"Hou","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B102","first-page":"1003","article-title":"Neuroinflammation induces neurodegeneration","volume":"1","author":"Kempuraj","year":"2016","journal-title":"J Neurol Neurosurg Spine"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.878987","article-title":"Microglial priming in infections and its risk to neurodegenerative diseases","volume":"16","author":"Lima","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17353","article-title":"Amelioration of signaling deficits underlying metabolic shortfall in TREM2R47H human iPSC-derived microglia","volume":"292","author":"Vasilopoulou","year":"2025","journal-title":"FEBS J"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.12.011","article-title":"Fructose-1,6-bisphosphate attenuates induction of nitric oxide synthase in microglia stimulated with lipopolysaccharide","volume":"90","author":"Kim","year":"2012","journal-title":"Life Sci"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.10.017","article-title":"Pyruvate kinase M2 (PKM2) interacts with activating transcription factor 2 (ATF2) to bridge glycolysis and pyroptosis in microglia","volume":"140","author":"Li","year":"2021","journal-title":"Mol Immunol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-023-01376-y","article-title":"Microglial metabolic reprogramming: emerging insights and therapeutic strategies in neurodegenerative diseases","volume":"43","author":"Miao","year":"2023","journal-title":"Cell Mol Neurobiol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11120854","article-title":"Diethyl succinate modulates microglial polarization and activation by reducing mitochondrial fission and cellular ROS","volume":"11","author":"Wang","year":"2021","journal-title":"Metabolites"},{"key":"B109","doi-asserted-by":"publisher","first-page":"e0136322","DOI":"10.1128\/jvi.01363-22","article-title":"Redox regulation and metabolic dependency of zika virus replication: inhibition by nrf2-antioxidant response and NAD(H) antimetabolites","volume":"97","author":"Sahoo","year":"2023","journal-title":"J Virol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1186\/s12879-022-07642-6","article-title":"2-deoxy-D-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial","volume":"22","author":"Bhatt","year":"2022","journal-title":"BMC Infect Dis"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01240-0","article-title":"A TREM2-activating antibody with a blood\u2013brain barrier transport vehicle enhances microglial metabolism in Alzheimer\u2019s disease models","volume":"26","author":"Lengerich","year":"2023","journal-title":"Nat Neurosci"},{"key":"B112","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.pneurobio.2007.02.010","article-title":"Radial glial cell heterogeneity\u2013the source of diverse progeny in the CNS","volume":"83","author":"Pinto","year":"2007","journal-title":"Prog Neurobiol"},{"key":"B113","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nmeth.3629","article-title":"Fixed single-cell transcriptomic characterization of human radial glial diversity","volume":"13","author":"Thomsen","year":"2016","journal-title":"Nat Methods"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.649538","article-title":"Growing glia: cultivating human stem cell models of gliogenesis in health and disease","volume":"9","author":"Lanjewar","year":"2021","journal-title":"Front Immunol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01024","article-title":"Interaction of microglia and astrocytes in the neurovascular unit","volume":"11","author":"Liu","year":"2020","journal-title":"Front Immunol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1177\/1073858418783959","article-title":"Microglia-astrocyte crosstalk: an intimate molecular conversation","volume":"25","author":"Jha","year":"2019","journal-title":"Neuroscientist"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1686774\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:17:35Z","timestamp":1766121455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1686774\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":116,"alternative-id":["10.3389\/fimmu.2025.1686774"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1686774","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"article-number":"1686774"}}