{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:19:28Z","timestamp":1783433968795,"version":"3.54.6"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurosci. Bull."],"DOI":"10.1007\/s12264-026-01657-8","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:49:55Z","timestamp":1783428595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysfunctional Mitochondria in Microglia Drive Cognitive Aging and Neurodegeneration via cGAS\u2013STING"],"prefix":"10.1007","author":[{"given":"Guanqin","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Xiong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8633-3388","authenticated-orcid":false,"given":"Xiaochun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"1657_CR1","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.immuni.2017.08.009","volume":"47","author":"GS Hotamisligil","year":"2017","unstructured":"Hotamisligil GS. Foundations of immunometabolism and implications for metabolic health and disease. Immunity 2017, 47: 406\u2013420.","journal-title":"Immunity"},{"key":"1657_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nrrheum.2017.54","volume":"13","author":"JP Rhoads","year":"2017","unstructured":"Rhoads JP, Major AS, Rathmell JC. Fine tuning of immunometabolism for the treatment of rheumatic diseases. Nat Rev Rheumatol 2017, 13: 313\u2013320.","journal-title":"Nat Rev Rheumatol"},{"key":"1657_CR3","doi-asserted-by":"crossref","unstructured":"Wang A, Luan HH, Medzhitov R. An evolutionary perspective on immunometabolism. Science 2019, 363: eaar3932.","DOI":"10.1126\/science.aar3932"},{"key":"1657_CR4","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1126\/science.aax0860","volume":"368","author":"G Desd\u00edn-Mic\u00f3","year":"2020","unstructured":"Desd\u00edn-Mic\u00f3 G, Soto-Heredero G, Aranda JF, Oller J, Carrasco E, Gaband\u00e9-Rodr\u00edguez E. T cells with dysfunctional mitochondria induce multimorbidity and premature senescence. Science 2020, 368: 1371\u20131376.","journal-title":"Science"},{"key":"1657_CR5","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.immuni.2023.01.011","volume":"56","author":"SK Wculek","year":"2023","unstructured":"Wculek SK, Heras-Murillo I, Mastrangelo A, Ma\u00f1anes D, Gal\u00e1n M, Miguel V, et al. Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis. Immunity 2023, 56: 516-530.e9.","journal-title":"Immunity"},{"key":"1657_CR6","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41586-021-03547-7","volume":"594","author":"MJ Yousefzadeh","year":"2021","unstructured":"Yousefzadeh MJ, Flores RR, Zhu Y, Schmiechen ZC, Brooks RW, Trussoni CE, et al. An aged immune system drives senescence and ageing of solid organs. Nature 2021, 594: 100\u2013105.","journal-title":"Nature"},{"key":"1657_CR7","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","volume":"8","author":"W Chen","year":"2023","unstructured":"Chen W, Zhao H, Li Y. Mitochondrial dynamics in health and disease: Mechanisms and potential targets. Sig Transduct Target Ther 2023, 8: 333.","journal-title":"Sig Transduct Target Ther"},{"key":"1657_CR8","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1038\/ni.3704","volume":"18","author":"EL Mills","year":"2017","unstructured":"Mills EL, Kelly B, O\u2019Neill LAJ. Mitochondria are the powerhouses of immunity. Nat Immunol 2017, 18: 488\u2013498.","journal-title":"Nat Immunol"},{"key":"1657_CR9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature08097","volume":"460","author":"EL Pearce","year":"2009","unstructured":"Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009, 460: 103\u2013107.","journal-title":"Nature"},{"key":"1657_CR10","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.immuni.2012.10.020","volume":"38","author":"LA Sena","year":"2013","unstructured":"Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013, 38: 225\u2013236.","journal-title":"Immunity"},{"key":"1657_CR11","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/j.cmet.2017.05.007","volume":"25","author":"TN Tarasenko","year":"2017","unstructured":"Tarasenko TN, Pacheco SE, Koenig MK, Gomez-Rodriguez J, Kapnick SM, Diaz F, et al. Cytochrome c oxidase activity is a metabolic checkpoint that regulates cell fate decisions during T cell activation and differentiation. Cell Metab 2017, 25: 1254-1268.e7.","journal-title":"Cell Metab"},{"key":"1657_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41586-018-0846-z","volume":"565","author":"SE Weinberg","year":"2019","unstructured":"Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM, Mart\u00ednez-Reyes I, et al. Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature 2019, 565: 495\u2013499.","journal-title":"Nature"},{"key":"1657_CR13","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1016\/j.cell.2022.05.017","volume":"185","author":"J Tcw","year":"2022","unstructured":"Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, et al. Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell 2022, 185: 2213-2233.e25.","journal-title":"Cell"},{"key":"1657_CR14","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/ni.3415","volume":"17","author":"CH Chang","year":"2016","unstructured":"Chang CH, Pearce EL. Emerging concepts of T cell metabolism as a target of immunotherapy. Nat Immunol 2016, 17: 364\u2013368.","journal-title":"Nat Immunol"},{"key":"1657_CR15","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41591-020-0815-6","volume":"26","author":"ECB Johnson","year":"2020","unstructured":"Johnson ECB, Dammer EB, Duong DM, Ping L, Zhou M, Yin L, et al. Large-scale proteomic analysis of Alzheimer\u2019s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat Med 2020, 26: 769\u2013780.","journal-title":"Nat Med"},{"key":"1657_CR16","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/s42255-023-00756-4","volume":"5","author":"Y Mi","year":"2023","unstructured":"Mi Y, Qi G, Vitali F, Shang Y, Raikes AC, Wang T, et al. Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. Nat Metab 2023, 5: 445\u2013465.","journal-title":"Nat Metab"},{"key":"1657_CR17","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/s42255-022-00643-4","volume":"4","author":"L Leng","year":"2022","unstructured":"Leng L, Yuan Z, Pan R, Su X, Wang H, Xue J, et al. Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to \u03b2-amyloid clearance. Nat Metab 2022, 4: 1287\u20131305.","journal-title":"Nat Metab"},{"key":"1657_CR18","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","volume":"79","author":"SA Wolf","year":"2017","unstructured":"Wolf SA, Boddeke HWGM, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol 2017, 79: 619\u2013643.","journal-title":"Annu Rev Physiol"},{"key":"1657_CR19","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.neuron.2021.01.027","volume":"109","author":"S Safaiyan","year":"2021","unstructured":"Safaiyan S, Besson-Girard S, Kaya T, Cantuti-Castelvetri L, Liu L, Ji H, et al. White matter aging drives microglial diversity. Neuron 2021, 109: 1100-1117.e10.","journal-title":"Neuron"},{"key":"1657_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.chom.2012.03.005","volume":"11","author":"T Kramer","year":"2012","unstructured":"Kramer T, Enquist LW. Alphaherpesvirus infection disrupts mitochondrial transport in neurons. Cell Host Microbe 2012, 11: 504\u2013514.","journal-title":"Cell Host Microbe"},{"key":"1657_CR21","doi-asserted-by":"publisher","first-page":"13348","DOI":"10.1038\/ncomms13348","volume":"7","author":"LS Reinert","year":"2016","unstructured":"Reinert LS, Lopu\u0161n\u00e1 K, Winther H, Sun C, Thomsen MK, Nandakumar R, et al. Sensing of HSV-1 by the cGAS\u2013STING pathway in microglia orchestrates antiviral defence in the CNS. Nat Commun 2016, 7: 13348.","journal-title":"Nat Commun"},{"key":"1657_CR22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136824","volume":"131","author":"LS Reinert","year":"2021","unstructured":"Reinert LS, Rashidi AS, Tran DN, Katzilieris-Petras G, Hvidt AK, Gohr M, et al. Brain immune cells undergo cGAS\/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production. J Clin Investig 2021, 131: e136824.","journal-title":"J Clin Investig"},{"key":"1657_CR23","doi-asserted-by":"crossref","unstructured":"Fruhw\u00fcrth S, Reinert LS, \u00d6berg C, Sakr M, Henricsson M, Zetterberg H, et al. TREM2 is down-regulated by HSV1 in microglia and involved in antiviral defense in the brain. Sci Adv 2023, 9: eadf5808.","DOI":"10.1126\/sciadv.adf5808"},{"key":"1657_CR24","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-06373-1","volume":"620","author":"MF Gulen","year":"2023","unstructured":"Gulen MF, Samson N, Keller A, Schwabenland M, Liu C, Gl\u00fcck S, et al. cGAS\u2013STING drives ageing-related inflammation and neurodegeneration. Nature 2023, 620: 374\u2013380.","journal-title":"Nature"},{"key":"1657_CR25","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41593-023-01315-6","volume":"26","author":"JC Udeochu","year":"2023","unstructured":"Udeochu JC, Amin S, Huang Y, Fan L, Torres ERS, Carling GK, et al. Tau activation of microglial cGAS\u2013IFN reduces MEF2C-mediated cognitive resilience. Nat Neurosci 2023, 26: 737\u2013750.","journal-title":"Nat Neurosci"},{"key":"1657_CR26","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s43587-022-00337-2","volume":"3","author":"X Xie","year":"2023","unstructured":"Xie X, Ma G, Li X, Zhao J, Zhao Z, Zeng J. Activation of innate immune cGAS-STING pathway contributes to Alzheimer\u2019s pathogenesis in 5 \u00d7 FAD mice. Nat Aging 2023, 3: 202\u2013212.","journal-title":"Nat Aging"},{"key":"1657_CR27","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1016\/j.cmet.2021.10.010","volume":"33","author":"D Erny","year":"2021","unstructured":"Erny D, Dokalis N, Mez\u00f6 C, Castoldi A, Mossad O, Staszewski O, et al. Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease. Cell Metab 2021, 33: 2260-2276.e7.","journal-title":"Cell Metab"},{"key":"1657_CR28","doi-asserted-by":"crossref","unstructured":"March-Diaz R, Lara-Ure\u00f1a N, Romero-Molina C, Heras-Garvin A, Ortega-de San Luis C, Alvarez-Vergara MI, et al. Hypoxia compromises the mitochondrial metabolism of Alzheimer\u2019s disease microglia via HIF1. Nat Aging 2021, 1: 385\u2013399.","DOI":"10.1038\/s43587-021-00054-2"},{"key":"1657_CR29","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/s42255-021-00483-8","volume":"3","author":"CD Wiley","year":"2021","unstructured":"Wiley CD, Campisi J. The metabolic roots of senescence: Mechanisms and opportunities for intervention. Nat Metab 2021, 3: 1290\u20131301.","journal-title":"Nat Metab"},{"key":"1657_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009822","volume":"17","author":"R Filograna","year":"2021","unstructured":"Filograna R, Lee S, Tiklov\u00e1 K, Mennuni M, Jonsson V, Ringn\u00e9r M, et al. Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response. PLoS Genet 2021, 17: e1009822.","journal-title":"PLoS Genet"},{"key":"1657_CR31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cmet.2016.09.017","volume":"25","author":"TES Kauppila","year":"2017","unstructured":"Kauppila TES, Kauppila JHK, Larsson NG. Mammalian mitochondria and aging: An update. Cell Metab 2017, 25: 57\u201371.","journal-title":"Cell Metab"},{"key":"1657_CR32","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41593-022-01027-3","volume":"25","author":"O Mossad","year":"2022","unstructured":"Mossad O, Batut B, Yilmaz B, Dokalis N, Mez\u00f6 C, Nent E, et al. Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine. Nat Neurosci 2022, 25: 295\u2013305.","journal-title":"Nat Neurosci"},{"key":"1657_CR33","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","volume":"61","author":"N Sun","year":"2016","unstructured":"Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell 2016, 61: 654\u2013666.","journal-title":"Mol Cell"},{"key":"1657_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102775","volume":"20","author":"RSJ Manuel","year":"2021","unstructured":"Manuel RSJ, Liang Y. Sexual dimorphism in immunometabolism and autoimmunity: Impact on personalized medicine. Autoimmun Rev 2021, 20: 102775.","journal-title":"Autoimmun Rev"},{"key":"1657_CR35","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.stem.2020.07.012","volume":"27","author":"J Zeng","year":"2020","unstructured":"Zeng J, Dong S, Luo Z, Xie X, Fu B, Li P, et al. The zika virus capsid disrupts corticogenesis by suppressing dicer activity and miRNA biogenesis. Cell Stem Cell 2020, 27: 618-632.e9.","journal-title":"Cell Stem Cell"},{"key":"1657_CR36","unstructured":"Zeng J, Xie X, Feng XL, Xu L, Han JB, Yu D, et al. Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice. eBioMedicine 2022, 75: 103803."},{"key":"1657_CR37","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM III, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell 2021, 184: 3573-3587.e29.","journal-title":"Cell"},{"key":"1657_CR38","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM III, et al. Comprehensive integration of single-cell data. Cell 2019, 177: 1888-1902.e21.","journal-title":"Cell"},{"key":"1657_CR39","doi-asserted-by":"crossref","unstructured":"Hu C, Li T, Xu Y, Zhang X, Li F, Bai J, et al. CellMarker 2.0: An updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data. Nucleic Acids Res 2023, 51: D870\u2013D876.","DOI":"10.1093\/nar\/gkac947"},{"key":"1657_CR40","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/s43587-023-00479-x","volume":"3","author":"X Li","year":"2023","unstructured":"Li X, Li Y, Jin Y, Zhang Y, Wu J, Xu Z, et al. Transcriptional and epigenetic decoding of the microglial aging process. Nat Aging 2023, 3: 1288\u20131311.","journal-title":"Nat Aging"},{"key":"1657_CR41","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1016\/j.neuron.2021.05.020","volume":"109","author":"D Lall","year":"2021","unstructured":"Lall D, Lorenzini I, Mota TA, Bell S, Mahan TE, Ulrich JD, et al. C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation. Neuron 2021, 109: 2275-2291.e8.","journal-title":"Neuron"},{"key":"1657_CR42","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41586-019-1088-4","volume":"568","author":"JV Pluvinage","year":"2019","unstructured":"Pluvinage JV, Haney MS, Smith BAH, Sun J, Iram T, Bonanno L, et al. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature 2019, 568: 187\u2013192.","journal-title":"Nature"},{"key":"1657_CR43","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1177\/0271678X20925655","volume":"40","author":"L Shi","year":"2020","unstructured":"Shi L, Rocha M, Zhang W, Jiang M, Li S, Ye Q, et al. Genome-wide transcriptomic analysis of microglia reveals impaired responses in aged mice after cerebral ischemia. J Cereb Blood Flow Metab 2020, 40: S49\u2013S66.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1657_CR44","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1038\/s41593-019-0491-3","volume":"22","author":"M Ximerakis","year":"2019","unstructured":"Ximerakis M, Lipnick SL, Innes BT, Simmons SK, Adiconis X, Dionne D, et al. Single-cell transcriptomic profiling of the aging mouse brain. Nat Neurosci 2019, 22: 1696\u20131708.","journal-title":"Nat Neurosci"},{"key":"1657_CR45","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1111\/jnc.14860","volume":"151","author":"DM Angelova","year":"2019","unstructured":"Angelova DM, Brown DR. Microglia and the aging brain: Are senescent microglia the key to neurodegeneration? J Neurochem 2019, 151: 676\u2013688.","journal-title":"J Neurochem"},{"key":"1657_CR46","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1093\/hmg\/ddh109","volume":"13","author":"MI Ekstrand","year":"2004","unstructured":"Ekstrand MI. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 2004, 13: 935\u2013944.","journal-title":"Hum Mol Genet"},{"key":"1657_CR47","doi-asserted-by":"publisher","first-page":"8624","DOI":"10.1523\/JNEUROSCI.1957-08.2008","volume":"28","author":"Y Hayashi","year":"2008","unstructured":"Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Ochi-Shindou M, et al. Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. J Neurosci 2008, 28: 8624\u20138634.","journal-title":"J Neurosci"},{"key":"1657_CR48","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","volume":"28","author":"A Hernandez-Segura","year":"2018","unstructured":"Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol 2018, 28: 436\u2013453.","journal-title":"Trends Cell Biol"},{"key":"1657_CR49","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.tins.2020.10.008","volume":"44","author":"BD Paul","year":"2021","unstructured":"Paul BD, Snyder SH, Bohr VA. Signaling by cGAS\u2013STING in neurodegeneration, neuroinflammation, and aging. Trends Neurosci 2021, 44: 83\u201396.","journal-title":"Trends Neurosci"},{"key":"1657_CR50","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.cell.2015.10.067","volume":"163","author":"Z Zhao","year":"2015","unstructured":"Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell 2015, 163: 1064\u20131078.","journal-title":"Cell"},{"key":"1657_CR51","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12306","volume":"498","author":"A Ablasser","year":"2013","unstructured":"Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, R\u00f6hl I, et al. cGAS produces a 2\u2032-5\u2032-linked cyclic dinucleotide second messenger that activates STING. Nature 2013, 498: 380\u2013384.","journal-title":"Nature"},{"key":"1657_CR52","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.cell.2013.04.046","volume":"153","author":"P Gao","year":"2013","unstructured":"Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, et al. Cyclic [G(2\u2032, 5\u2032)pA(3\u2032, 5\u2032)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell 2013, 153: 1094\u20131107.","journal-title":"Cell"},{"key":"1657_CR53","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","volume":"461","author":"H Ishikawa","year":"2009","unstructured":"Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009, 461: 788\u2013792.","journal-title":"Nature"},{"key":"1657_CR54","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","volume":"339","author":"L Sun","year":"2013","unstructured":"Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013, 339: 786\u2013791.","journal-title":"Science"},{"key":"1657_CR55","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1126\/science.1229963","volume":"339","author":"J Wu","year":"2013","unstructured":"Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 2013, 339: 826\u2013830.","journal-title":"Science"},{"key":"1657_CR56","doi-asserted-by":"crossref","unstructured":"Ablasser A, Chen ZJ. cGAS in action: Expanding roles in immunity and inflammation. Science 2019, 363: eaat8657.","DOI":"10.1126\/science.aat8657"},{"key":"1657_CR57","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.molcel.2014.03.040","volume":"54","author":"X Cai","year":"2014","unstructured":"Cai X, Chiu YH, Chen ZJ. The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol Cell 2014, 54: 289\u2013296.","journal-title":"Mol Cell"},{"key":"1657_CR58","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nature14156","volume":"520","author":"AP West","year":"2015","unstructured":"West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520: 553\u2013557.","journal-title":"Nature"},{"key":"1657_CR59","doi-asserted-by":"publisher","first-page":"E4612","DOI":"10.1073\/pnas.1705499114","volume":"114","author":"H Yang","year":"2017","unstructured":"Yang H, Wang H, Ren J, Chen Q, Chen ZJ. cGAS is essential for cellular senescence. Proc Natl Acad Sci U S A 2017, 114: E4612\u2013E4620.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1657_CR60","doi-asserted-by":"crossref","unstructured":"Li Q, Cao Y, Dang C, Han B, Han R, Ma H, et al. Inhibition of double\u2010strand DNA\u2010sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol Med 2020, 12: EMMM201911002.","DOI":"10.15252\/emmm.201911002"},{"key":"1657_CR61","doi-asserted-by":"publisher","first-page":"15989","DOI":"10.1073\/pnas.2002144117","volume":"117","author":"M Sharma","year":"2020","unstructured":"Sharma M, Rajendrarao S, Shahani N, Ram\u00edrez-Jarqu\u00edn UN, Subramaniam S. Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease. Proc Natl Acad Sci U S A 2020, 117: 15989\u201315999.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1657_CR62","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1093\/brain\/awaa246","volume":"143","author":"M Borsche","year":"2020","unstructured":"Borsche M, K\u00f6nig IR, Delcambre S, Petrucci S, Balck A, Br\u00fcggemann N, et al. Mitochondrial damage-associated inflammation highlights biomarkers in PRKN\/PINK1 Parkinsonism. Brain 2020, 143: 3041\u20133051.","journal-title":"Brain"},{"key":"1657_CR63","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","volume":"183","author":"CH Yu","year":"2020","unstructured":"Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, et al. TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS\/STING in ALS. Cell 2020, 183: 636-649.e18.","journal-title":"Cell"},{"key":"1657_CR64","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nature21363","volume":"542","author":"GS Hotamisligil","year":"2017","unstructured":"Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature 2017, 542: 177\u2013185.","journal-title":"Nature"},{"key":"1657_CR65","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","volume":"27","author":"MP Mattson","year":"2018","unstructured":"Mattson MP, Arumugam TV. Hallmarks of brain aging: Adaptive and pathological modification by metabolic states. Cell Metab 2018, 27: 1176\u20131199.","journal-title":"Cell Metab"},{"key":"1657_CR66","doi-asserted-by":"publisher","first-page":"1242454","DOI":"10.1126\/science.1242454","volume":"342","author":"EL Pearce","year":"2013","unstructured":"Pearce EL, Poffenberger MC, Chang CH, Jones RG. Fueling immunity: Insights into metabolism and lymphocyte function. Science 2013, 342: 1242454.","journal-title":"Science"},{"key":"1657_CR67","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","volume":"169","author":"MD Buck","year":"2017","unstructured":"Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic instruction of immunity. Cell 2017, 169: 570\u2013586.","journal-title":"Cell"},{"key":"1657_CR68","doi-asserted-by":"publisher","first-page":"3966","DOI":"10.1038\/s41380-023-02289-4","volume":"28","author":"L Naia","year":"2023","unstructured":"Naia L, Shimozawa M, Bereczki E, Li X, Liu J, Jiang R, et al. Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models. Mol Psychiatry 2023, 28: 3966\u20133981.","journal-title":"Mol Psychiatry"},{"key":"1657_CR69","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cell.2017.12.025","volume":"172","author":"YS Lee","year":"2018","unstructured":"Lee YS, Wollam J, Olefsky JM. An integrated view of immunometabolism. Cell 2018, 172: 22\u201340.","journal-title":"Cell"},{"key":"1657_CR70","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","volume":"213","author":"LAJ O\u2019Neill","year":"2016","unstructured":"O\u2019Neill LAJ, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med 2016, 213: 15\u201323.","journal-title":"J Exp Med"},{"key":"1657_CR71","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1016\/j.tcb.2017.07.005","volume":"27","author":"SA Nish","year":"2017","unstructured":"Nish SA, Lin WW, Reiner SL. Lymphocyte fate and metabolism: A clonal balancing act. Trends Cell Biol 2017, 27: 946\u2013954.","journal-title":"Trends Cell Biol"}],"container-title":["Neuroscience Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01657-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12264-026-01657-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12264-026-01657-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:03:24Z","timestamp":1783433004000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12264-026-01657-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":71,"alternative-id":["1657"],"URL":"https:\/\/doi.org\/10.1007\/s12264-026-01657-8","relation":{},"ISSN":["1673-7067","1995-8218"],"issn-type":[{"value":"1673-7067","type":"print"},{"value":"1995-8218","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"20 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}