{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T23:51:00Z","timestamp":1784937060322,"version":"3.55.0"},"reference-count":112,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007780","name":"Indian Institute of Science","doi-asserted-by":"crossref","award":["EMSTAR\/2023\/SL03"],"award-info":[{"award-number":["EMSTAR\/2023\/SL03"]}],"id":[{"id":"10.13039\/100007780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"crossref","award":["BT\/INF\/22\/SP17358\/2016"],"award-info":[{"award-number":["BT\/INF\/22\/SP17358\/2016"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007116","name":"Indian Institute of Science Education and Research Pune","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007116","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor function. Here, we developed a Drosophila model of ALS8 (VAPBP58S) using CRISPR\/Cas9 genome editing. VAPB is an endoplasmic reticulum-based adapter protein associated with and regulating intracellular membrane:membrane contact sites. VAPBP58S flies showed progressive age-dependent motor deficits and a shortened lifespan, paralleling features of the human disease. VAPBP58S brains exhibited age-dependent neuroinflammation, as measured by whole-transcriptome quantitative mRNA sequencing, suggesting a broad, low-grade enhancement of signalling across multiple immune pathways (Toll, Imd, Jak-STAT and c-Jun). Our results indicated that glial cells in the brain are the site of brain inflammation and identified the Drosophila orthologue of Fos (Kayak) as a key modulator of age-dependent inflammation. In accordance, we found that overexpression of wild-type kayak or its dominant-active variant kayakK357R in glia reduced inflammation and, concomitantly, improved motor function. In contrast, knockdown of glial kayak accelerated age-dependent deterioration of motor function and enhanced neuroinflammation. Our study underscores the roles of glial-modulated brain inflammation in dictating ALS8 progression and identifies kayak as a central negative regulator of neuroinflammation in disease.<\/jats:p>","DOI":"10.1242\/dmm.052810","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:03:54Z","timestamp":1780560234000},"source":"Crossref","is-referenced-by-count":1,"title":["Fos regulates age-dependent neuroinflammation in a\n                    <i>VAPP58S<\/i>\n                    model of amyotrophic lateral sclerosis"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-3911","authenticated-orcid":false,"given":"Namrata Pramod","family":"Kulkarni","sequence":"first","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-3308","authenticated-orcid":false,"given":"Aparna","family":"Thulasidharan","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-6121","authenticated-orcid":false,"given":"Amarendranath","family":"Soory","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6436-1597","authenticated-orcid":false,"given":"Pulkit","family":"Goel","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-9035","authenticated-orcid":false,"given":"Sanhita","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1008-8455","authenticated-orcid":false,"given":"Vidyadheesh","family":"Kelkar","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-3140","authenticated-orcid":false,"given":"Girish S.","family":"Ratnaparkhi","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Department of Biology , , Pune 411008 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"2026072407543211300_DMM052810C1","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1002\/humu.22157","article-title":"ALSoD: a user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics","volume":"33","author":"Abel","year":"2012","journal-title":"Hum. Mutat."},{"key":"2026072407543211300_DMM052810C2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.mod.2018.05.006","article-title":"Fos metamorphoses: lessons from mutants in model organisms","volume":"154","author":"Alfonso-Gonzalez","year":"2018","journal-title":"Mech. Dev."},{"key":"2026072407543211300_DMM052810C3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1126\/science.aat0473","article-title":"Glia as architects of central nervous system formation and function","volume":"362","author":"Allen","year":"2018","journal-title":"Science"},{"key":"2026072407543211300_DMM052810C4","doi-asserted-by":"publisher","first-page":"1671906","DOI":"10.3389\/fnmol.2025.1671906","article-title":"C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review","volume":"18","author":"Almalki","year":"2025","journal-title":"Front. Mol. Neurosci."},{"key":"2026072407543211300_DMM052810C5","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.1093\/hmg\/ddu055","article-title":"Identification of ter94, Drosophila VCP, as a strong modulator of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS","volume":"23","author":"Azuma","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"2026072407543211300_DMM052810C6","doi-asserted-by":"publisher","first-page":"16021","DOI":"10.1073\/pnas.0607423103","article-title":"Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis","volume":"103","author":"Beers","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026072407543211300_DMM052810C7","doi-asserted-by":"publisher","first-page":"15558","DOI":"10.1073\/pnas.0807419105","article-title":"CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS","volume":"105","author":"Beers","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026072407543211300_DMM052810C8","doi-asserted-by":"publisher","first-page":"100689","DOI":"10.1016\/j.xpro.2021.100689","article-title":"A protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using advanced microscopy","volume":"2","author":"Behnke","year":"2021","journal-title":"STAR Protoc."},{"key":"2026072407543211300_DMM052810C9","doi-asserted-by":"publisher","first-page":"RP104691","DOI":"10.7554\/eLife.104691.3","article-title":"Prefoldin 5 is a microtubule-associated protein that suppresses Tau aggregation and neurotoxicity","volume":"13","author":"Bisht","year":"2026","journal-title":"eLife"},{"key":"2026072407543211300_DMM052810C10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.exger.2010.11.003","article-title":"Regulation of Drosophila lifespan by JNK signaling","volume":"46","author":"Biteau","year":"2011","journal-title":"Exp. Gerontol."},{"key":"2026072407543211300_DMM052810C11","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/dneu.22737","article-title":"Neuron-glia interaction in the Drosophila nervous system","volume":"81","author":"Bittern","year":"2021","journal-title":"Dev. Neurobiol."},{"key":"2026072407543211300_DMM052810C12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.neuron.2006.09.018","article-title":"ALS: a disease of motor neurons and their nonneuronal neighbors","volume":"52","author":"Boill\u00e9e","year":"2006","journal-title":"Neuron"},{"key":"2026072407543211300_DMM052810C13","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/j.cmet.2021.07.006","article-title":"Astrocyte-neuron metabolic cooperation shapes brain activity","volume":"33","author":"Bonvento","year":"2021","journal-title":"Cell Metab."},{"key":"2026072407543211300_DMM052810C14","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.3390\/cells10081865","article-title":"The link between VAPB loss of function and amyotrophic lateral sclerosis","volume":"10","author":"Borgese","year":"2021","journal-title":"Cells"},{"key":"2026072407543211300_DMM052810C15","doi-asserted-by":"publisher","first-page":"25152564211022515","DOI":"10.1177\/25152564211022515","article-title":"Mutant VAPB: culprit or innocent bystander of amyotrophic lateral sclerosis?","volume":"4","author":"Borgese","year":"2021","journal-title":"Contact"},{"key":"2026072407543211300_DMM052810C16","doi-asserted-by":"publisher","first-page":"6964","DOI":"10.1128\/MCB.25.16.6964-6979.2005","article-title":"Down-regulation of c-Fos\/c-Jun AP-1 dimer activity by sumoylation","volume":"25","author":"Bossis","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"2026072407543211300_DMM052810C17","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.ncl.2015.07.001","article-title":"Familial amyotrophic lateral sclerosis","volume":"33","author":"Boylan","year":"2015","journal-title":"Neurol. Clin."},{"key":"2026072407543211300_DMM052810C18","doi-asserted-by":"publisher","first-page":"E1752","DOI":"10.1073\/pnas.1306220110","article-title":"Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain","volume":"110","author":"Cao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026072407543211300_DMM052810C19","doi-asserted-by":"publisher","first-page":"dmm033803","DOI":"10.1242\/dmm.033803","article-title":"SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in a Drosophila model of amyotrophic lateral sclerosis","volume":"12","author":"Chaplot","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"2026072407543211300_DMM052810C20","doi-asserted-by":"publisher","first-page":"17913","DOI":"10.1073\/pnas.0804610105","article-title":"T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS","volume":"105","author":"Chiu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026072407543211300_DMM052810C21","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/35097565","article-title":"From charcot to lou gehrig: deciphering selective motor neuron death in als","volume":"2","author":"Cleveland","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"2026072407543211300_DMM052810C22","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1242\/dev.152207","article-title":"The C. elegans VAPB homolog VPR-1 is a permissive signal for gonad development","volume":"144","author":"Cottee","year":"2017","journal-title":"Development"},{"key":"2026072407543211300_DMM052810C23","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS-STING pathway as a therapeutic target in inflammatory diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"2026072407543211300_DMM052810C24","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1242\/bio.201410066","article-title":"A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis","volume":"3","author":"Deivasigamani","year":"2014","journal-title":"Biol. Open"},{"key":"2026072407543211300_DMM052810C25","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/glia.23728","article-title":"The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins","volume":"68","author":"Deora","year":"2020","journal-title":"Glia"},{"key":"2026072407543211300_DMM052810C26","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.immuni.2024.02.019","article-title":"New frontiers in the cGAS-STING intracellular DNA-sensing pathway","volume":"57","author":"Dvorkin","year":"2024","journal-title":"Immunity"},{"key":"2026072407543211300_DMM052810C27","doi-asserted-by":"publisher","first-page":"108052","DOI":"10.1016\/j.isci.2023.108052","article-title":"Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling","volume":"26","author":"Elguero","year":"2023","journal-title":"iScience"},{"key":"2026072407543211300_DMM052810C28","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"2026072407543211300_DMM052810C29","doi-asserted-by":"publisher","first-page":"19796","DOI":"10.1038\/s41598-024-67165-9","article-title":"Inflammatory signature in amyotrophic lateral sclerosis predicting disease progression","volume":"14","author":"Femiano","year":"2024","journal-title":"Sci. Rep."},{"key":"2026072407543211300_DMM052810C30","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1126\/science.298.5593.556","article-title":"New insights into neuron-glia communication","volume":"298","author":"Fields","year":"2002","journal-title":"Science"},{"key":"2026072407543211300_DMM052810C31","doi-asserted-by":"publisher","first-page":"iyad004","DOI":"10.1093\/genetics\/iyad004","article-title":"A modERN resource: identification of Drosophila transcription factor candidate target genes using RNAi","volume":"223","author":"Fisher","year":"2023","journal-title":"Genetics"},{"key":"2026072407543211300_DMM052810C32","doi-asserted-by":"publisher","first-page":"7557","DOI":"10.1007\/s00415-024-12699-1","article-title":"Exploiting the role of CSF NfL, CHIT1, and miR-181b as potential diagnostic and prognostic biomarkers for ALS","volume":"271","author":"Gagliardi","year":"2024","journal-title":"J. Neurol."},{"key":"2026072407543211300_DMM052810C33","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1534\/genetics.105.045534","article-title":"A genetic screen targeting the tumor necrosis factor\/Eiger signaling pathway: identification of Drosophila TAB2 as a functionally conserved component","volume":"171","author":"Geuking","year":"2005","journal-title":"Genetics"},{"key":"2026072407543211300_DMM052810C111","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1471-2164-7-69","article-title":"Specific age-related signatures in Drosophila body parts transcriptome","volume":"7","author":"Girardot","year":"2006","journal-title":"BMC Genomics"},{"key":"2026072407543211300_DMM052810C34","doi-asserted-by":"publisher","first-page":"104837","DOI":"10.1016\/j.nbd.2020.104837","article-title":"Inactivation of Hippo and cJun-N-terminal Kinase (JNK) signaling mitigate FUS mediated neurodegeneration in vivo","volume":"140","author":"Gogia","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"2026072407543211300_DMM052810C35","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.devcel.2011.12.009","article-title":"Secreted VAPB\/ALS8 major sperm protein domains modulate mitochondrial localization and morphology via growth cone guidance receptors","volume":"22","author":"Han","year":"2012","journal-title":"Dev. Cell"},{"key":"2026072407543211300_DMM052810C112","doi-asserted-by":"publisher","first-page":"jkaf039","DOI":"10.1093\/g3journal\/jkaf039","article-title":"Dynamic changes in gene expression through aging in Drosophila melanogaster heads","volume":"15","author":"Hanson","year":"2025","journal-title":"G3"},{"key":"2026072407543211300_DMM052810C36","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/ana.10805","article-title":"Presence of dendritic cells, MCP-1, and activated microglia\/macrophages in amyotrophic lateral sclerosis spinal cord tissue","volume":"55","author":"Henkel","year":"2004","journal-title":"Ann. Neurol."},{"key":"2026072407543211300_DMM052810C37","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1093\/emboj\/cdf306","article-title":"Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway","volume":"21","author":"Igaki","year":"2002","journal-title":"EMBO J."},{"key":"2026072407543211300_DMM052810C38","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.3390\/cells10071780","article-title":"The interactome of the VAP family of proteins: an overview","volume":"10","author":"James","year":"2021","journal-title":"Cells"},{"key":"2026072407543211300_DMM052810C39","doi-asserted-by":"publisher","first-page":"eaea3996","DOI":"10.1126\/sciadv.aea3996","article-title":"VAPB is a negative regulator of STING-mediated innate immune signaling","volume":"11","author":"Ji","year":"2025","journal-title":"Sci. Adv."},{"key":"2026072407543211300_DMM052810C40","doi-asserted-by":"publisher","first-page":"102320","DOI":"10.1016\/j.arr.2024.102320","article-title":"Modulation of ER-mitochondria tethering complex VAPB-PTPIP51: Novel therapeutic targets for aging-associated diseases","volume":"98","author":"Jiang","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"2026072407543211300_DMM052810C41","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.immuni.2025.03.013","article-title":"Glia get RIPped in ALS","volume":"58","author":"Johnson","year":"2025","journal-title":"Immunity"},{"key":"2026072407543211300_DMM052810C42","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/jb\/mvz011","article-title":"Multiple functions of the ER-resident VAP and its extracellular role in neural development and disease","volume":"165","author":"Kamemura","year":"2019","journal-title":"J. Biochem."},{"key":"2026072407543211300_DMM052810C43","doi-asserted-by":"publisher","first-page":"E4152","DOI":"10.1073\/pnas.1316895110","article-title":"A Drosophila model of closed head traumatic brain injury","volume":"110","author":"Katzenberger","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026072407543211300_DMM052810C44","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.dci.2013.05.014","article-title":"The Drosophila IMD pathway in the activation of the humoral immune response","volume":"42","author":"Kleino","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"2026072407543211300_DMM052810C45","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1038\/sj.onc.1204300","article-title":"Drosophila AP-1: lessons from an invertebrate","volume":"20","author":"Kockel","year":"2001","journal-title":"Oncogene"},{"key":"2026072407543211300_DMM052810C46","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.3390\/molecules30061220","article-title":"Beyond static tethering at membrane contact sites: structural dynamics and functional implications of VAP proteins","volume":"30","author":"Kodama","year":"2025","journal-title":"Molecules"},{"key":"2026072407543211300_DMM052810C47","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1021\/acs.jproteome.4c00990","article-title":"Sex-specific markers of neuroinflammation and neurodegeneration in the spinal cord proteome of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis","volume":"24","author":"Koehn","year":"2025","journal-title":"J. Proteome Res."},{"key":"2026072407543211300_DMM052810C48","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1534\/genetics.113.156737","article-title":"Highly improved gene targeting by germline-specific Cas9 expression in Drosophila","volume":"195","author":"Kondo","year":"2013","journal-title":"Genetics"},{"key":"2026072407543211300_DMM052810C49","doi-asserted-by":"publisher","first-page":"895856","DOI":"10.3389\/fcell.2022.895856","article-title":"VAP proteins - from organelle tethers to pathogenic host interactors and their role in neuronal disease","volume":"10","author":"Kors","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"2026072407543211300_DMM052810C50","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.celrep.2017.04.007","article-title":"NF-kappa B immunity in the brain determines fly lifespan in healthy aging and age-related neurodegeneration","volume":"19","author":"Kounatidis","year":"2017","journal-title":"Cell Rep."},{"key":"2026072407543211300_DMM052810C51","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12974-020-01963-6","article-title":"The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response","volume":"17","author":"Lee","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"2026072407543211300_DMM052810C52","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s12974-018-1278-2","article-title":"Inhibition of NF-\u03baB in astrocytes is sufficient to delay neurodegeneration induced by proteotoxicity in neurons","volume":"15","author":"Li","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"2026072407543211300_DMM052810C53","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"2026072407543211300_DMM052810C54","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s00251-021-01239-0","article-title":"Sensing microbial infections in the Drosophila melanogaster genetic model organism","volume":"74","author":"Liegeois","year":"2022","journal-title":"Immunogenetics"},{"key":"2026072407543211300_DMM052810C55","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte crosstalk in CNS inflammation","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"2026072407543211300_DMM052810C56","doi-asserted-by":"publisher","first-page":"e52741","DOI":"10.3791\/52741","article-title":"Quantitative analysis of climbing defects in a Drosophila model of neurodegenerative disorders","author":"Madabattula","year":"2015","journal-title":"J. Vis. Exp."},{"key":"2026072407543211300_DMM052810C57","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3109\/17482968.2011.648644","article-title":"Juvenile and adult-onset ALS\/MND among Africans: incidence, phenotype, survival: a review","volume":"13","author":"Marin","year":"2012","journal-title":"Amyotroph Lateral Scler."},{"key":"2026072407543211300_DMM052810C58","doi-asserted-by":"publisher","first-page":"114678","DOI":"10.1016\/j.celrep.2024.114678","article-title":"An evolutionary perspective to innate antiviral immunity in animals","volume":"43","author":"Marques","year":"2024","journal-title":"Cell Rep."},{"key":"2026072407543211300_DMM052810C59","doi-asserted-by":"publisher","first-page":"e157161","DOI":"10.1172\/JCI157161","article-title":"Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury","volume":"132","author":"Martens","year":"2022","journal-title":"J. Clin. Invest."},{"key":"2026072407543211300_DMM052810C60","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.1016\/j.celrep.2018.05.029","article-title":"Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function","volume":"23","author":"Martin","year":"2018","journal-title":"Cell Rep."},{"key":"2026072407543211300_DMM052810C61","doi-asserted-by":"publisher","first-page":"jmedgenet-2020-106866","DOI":"10.1136\/jmedgenet-2020-106866","article-title":"Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis","volume":"58","author":"McCann","year":"2020","journal-title":"J. Med. Genet."},{"key":"2026072407543211300_DMM052810C62","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1186\/s12974-017-1028-x","article-title":"Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly pro-inflammatory responses in microglia","volume":"14","author":"Mishra","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"2026072407543211300_DMM052810C63","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1016\/S0140-6736(07)60944-1","article-title":"Amyotrophic lateral sclerosis","volume":"369","author":"Mitchell","year":"2007","journal-title":"Lancet"},{"key":"2026072407543211300_DMM052810C64","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1093\/hmg\/ddr284","article-title":"Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients","volume":"20","author":"Mitne-Neto","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2026072407543211300_DMM052810C65","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1093\/hmg\/ddt594","article-title":"The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control","volume":"23","author":"Moustaqim-Barrette","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"2026072407543211300_DMM052810C66","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.bbalip.2016.02.009","article-title":"VAP, a versatile access point for the endoplasmic reticulum: review and analysis of FFAT-like motifs in the VAPome","volume":"1861","author":"Murphy","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"2026072407543211300_DMM052810C67","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nn1876","article-title":"Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons","volume":"10","author":"Nagai","year":"2007","journal-title":"Nat. Neurosci."},{"key":"2026072407543211300_DMM052810C68","doi-asserted-by":"publisher","first-page":"25152564211012246","DOI":"10.1177\/25152564211012246","article-title":"What the VAP: the expanded VAP family of proteins interacting with FFAT and FFAT-related motifs for interorganellar contact","volume":"4","author":"Neefjes","year":"2021","journal-title":"Contact"},{"key":"2026072407543211300_DMM052810C69","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1086\/425287","article-title":"A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis","volume":"75","author":"Nishimura","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"2026072407543211300_DMM052810C70","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41586-023-06956-y","article-title":"Motion of VAPB molecules reveals ER-mitochondria contact site subdomains","volume":"626","author":"Obara","year":"2024","journal-title":"Nature"},{"key":"2026072407543211300_DMM052810C71","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1126\/science.aaf1064","article-title":"C9orf72 is required for proper macrophage and microglial function in mice","volume":"351","author":"O'Rourke","year":"2016","journal-title":"Science"},{"key":"2026072407543211300_DMM052810C72","doi-asserted-by":"publisher","first-page":"e0209405","DOI":"10.1371\/journal.pone.0209405","article-title":"Brain transcriptome changes in the aging Drosophila melanogaster accompany olfactory memory performance deficits","volume":"13","author":"Pacifico","year":"2018","journal-title":"PLoS ONE"},{"key":"2026072407543211300_DMM052810C73","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1056\/NEJMoa1916945","article-title":"Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis","volume":"383","author":"Paganoni","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2026072407543211300_DMM052810C74","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1101\/gad.1168104","article-title":"Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila","volume":"18","author":"Park","year":"2004","journal-title":"Genes Dev."},{"key":"2026072407543211300_DMM052810C75","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nrn1971","article-title":"Molecular biology of amyotrophic lateral sclerosis: insights from genetics","volume":"7","author":"Pasinelli","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"2026072407543211300_DMM052810C76","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0896-6273(02)00769-9","article-title":"Drosophila VAP-33A directs bouton formation at neuromuscular junctions in a dosage-dependent manner","volume":"35","author":"Pennetta","year":"2002","journal-title":"Neuron"},{"key":"2026072407543211300_DMM052810C77","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1101\/gad.4.5.822","article-title":"The Drosophila Fos-related AP-1 protein is a developmentally regulated transcription factor","volume":"4","author":"Perkins","year":"1990","journal-title":"Genes Dev."},{"key":"2026072407543211300_DMM052810C78","doi-asserted-by":"publisher","first-page":"e2334","DOI":"10.1371\/journal.pone.0002334","article-title":"A Drosophila model of ALS: human ALS-associated mutation in VAP33A suggests a dominant negative mechanism","volume":"3","author":"Ratnaparkhi","year":"2008","journal-title":"PLoS ONE"},{"key":"2026072407543211300_DMM052810C79","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1146\/annurev-biochem-083024-122821","article-title":"Lipid dynamics at membrane contact sites","volume":"94","author":"Reinisch","year":"2025","journal-title":"Annu. Rev. Biochem."},{"key":"2026072407543211300_DMM052810C80","doi-asserted-by":"publisher","first-page":"I1","DOI":"10.1007\/s004150050551","article-title":"Oxidative stress in amyotrophic lateral sclerosis","volume":"247","author":"Robberecht","year":"2000","journal-title":"J. Neurol."},{"key":"2026072407543211300_DMM052810C81","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1523\/JNEUROSCI.1799-22.2023","article-title":"c-Jun N-terminal kinase promotes stress granule assembly and neurodegeneration in C9orf72-mediated ALS and FTD","volume":"43","author":"Sahana","year":"2023","journal-title":"J. Neurosci."},{"key":"2026072407543211300_DMM052810C82","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2026072407543211300_DMM052810C83","doi-asserted-by":"publisher","first-page":"eadx0043","DOI":"10.1126\/science.adx0043","article-title":"Neuroinflammation across neurological diseases","volume":"388","author":"Shi","year":"2025","journal-title":"Science"},{"key":"2026072407543211300_DMM052810C84","doi-asserted-by":"publisher","first-page":"48928","DOI":"10.1074\/jbc.M304802200","article-title":"Immune activation of NF-kappaB and JNK requires Drosophila TAK1","volume":"278","author":"Silverman","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026072407543211300_DMM052810C85","doi-asserted-by":"publisher","first-page":"e1010356","DOI":"10.1371\/journal.ppat.1010356","article-title":"SUMOylation of Jun fine-tunes the Drosophila gut immune response","volume":"18","author":"Soory","year":"2022","journal-title":"PLoS Pathog."},{"key":"2026072407543211300_DMM052810C86","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1136\/jnnp-2017-317138","article-title":"Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression","volume":"89","author":"Steinacker","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2026072407543211300_DMM052810C87","doi-asserted-by":"publisher","first-page":"3996","DOI":"10.1038\/ncomms4996","article-title":"ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS\/FTD-associated TDP-43","volume":"5","author":"Stoica","year":"2014","journal-title":"Nat. Commun."},{"key":"2026072407543211300_DMM052810C88","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.imlet.2020.06.017","article-title":"JNK signaling in Drosophila immunity and homeostasis","volume":"226","author":"Tafesh-Edwards","year":"2020","journal-title":"Immunol. Lett."},{"key":"2026072407543211300_DMM052810C89","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1001\/archneur.64.2.232","article-title":"Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up","volume":"64","author":"Tartaglia","year":"2007","journal-title":"Arch. Neurol."},{"key":"2026072407543211300_DMM052810C90","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1093\/hmg\/ddac076","article-title":"Caspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD\/NF\u03baB-mediated glial inflammation in a Drosophila model of human disease","volume":"31","author":"Tendulkar","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"2026072407543211300_DMM052810C91","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/WCO.0000000000000599","article-title":"Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis","volume":"31","author":"Thonhoff","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"2026072407543211300_DMM052810C92","doi-asserted-by":"publisher","first-page":"106517","DOI":"10.1016\/j.nbd.2024.106517","article-title":"Age-dependent dynamics of neuronal VAPB(ALS) inclusions in the adult brain","volume":"196","author":"Thulasidharan","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"2026072407543211300_DMM052810C93","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.exger.2010.09.002","article-title":"Heat shock proteins and Drosophila aging","volume":"46","author":"Tower","year":"2011","journal-title":"Exp. Gerontol."},{"key":"2026072407543211300_DMM052810C94","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1523\/JNEUROSCI.16-03-00877.1996","article-title":"Metabolic coupling between glia and neurons","volume":"16","author":"Tsacopoulos","year":"1996","journal-title":"J. Neurosci."},{"key":"2026072407543211300_DMM052810C95","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.cell.2008.04.039","article-title":"The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors","volume":"133","author":"Tsuda","year":"2008","journal-title":"Cell"},{"key":"2026072407543211300_DMM052810C96","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1177\/0748730412462206","article-title":"Pigment-dispersing factor is involved in age-dependent rhythm changes in Drosophila melanogaster","volume":"27","author":"Umezaki","year":"2012","journal-title":"J. Biol. Rhythms"},{"key":"2026072407543211300_DMM052810C97","doi-asserted-by":"publisher","first-page":"e0261087","DOI":"10.1371\/journal.pone.0261087","article-title":"Age-related changes in Kv4\/Shal and Kv1\/Shaker expression in Drosophila and a role for reactive oxygen species","volume":"16","author":"Vallejos","year":"2021","journal-title":"PLoS ONE"},{"key":"2026072407543211300_DMM052810C98","doi-asserted-by":"publisher","first-page":"e3001456","DOI":"10.1371\/journal.pbio.3001456","article-title":"Glial immune-related pathways mediate effects of closed head traumatic brain injury on behavior and lethality in Drosophila","volume":"20","author":"van Alphen","year":"2022","journal-title":"PLoS Biol."},{"key":"2026072407543211300_DMM052810C99","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1101\/gad.203301","article-title":"Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel\/NF-\u03baB-dependent innate immune responses","volume":"15","author":"Vidal","year":"2001","journal-title":"Genes Dev."},{"key":"2026072407543211300_DMM052810C100","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cell.2023.11.040","article-title":"Making the connection: how membrane contact sites have changed our view of organelle biology","volume":"187","author":"Voeltz","year":"2024","journal-title":"Cell"},{"key":"2026072407543211300_DMM052810C101","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.cmet.2015.07.006","article-title":"Glial glycolysis is essential for neuronal survival in Drosophila","volume":"22","author":"Volkenhoff","year":"2015","journal-title":"Cell Metab."},{"key":"2026072407543211300_DMM052810C102","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1002\/glia.20062","article-title":"Increased cytotoxic potential of microglia from ALS-transgenic mice","volume":"48","author":"Weydt","year":"2004","journal-title":"Glia"},{"key":"2026072407543211300_DMM052810C103","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1750-1172-4-3","article-title":"Amyotrophic lateral sclerosis","volume":"4","author":"Wijesekera","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"2026072407543211300_DMM052810C104","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41423-025-01275-w","article-title":"NLRP3 inflammasome in neuroinflammation and central nervous system diseases","volume":"22","author":"Xu","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"2026072407543211300_DMM052810C105","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nn2047","article-title":"Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis","volume":"11","author":"Yamanaka","year":"2008","journal-title":"Nat. Neurosci."},{"key":"2026072407543211300_DMM052810C106","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1080\/17482960600881870","article-title":"Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study)","volume":"7","author":"Yoshino","year":"2006","journal-title":"Amyotroph Lateral Scler."},{"key":"2026072407543211300_DMM052810C107","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ydbio.2020.10.015","article-title":"The type II integral ER membrane protein VAP-B homolog in C. elegans is cleaved to release the N-terminal MSP domain to signal non-cell-autonomously","volume":"470","author":"Zein-Sabatto","year":"2021","journal-title":"Dev. Biol."},{"key":"2026072407543211300_DMM052810C108","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"2026072407543211300_DMM052810C109","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s11481-013-9489-x","article-title":"Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis","volume":"8","author":"Zhao","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"2026072407543211300_DMM052810C110","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.cub.2018.03.002","article-title":"The ER contact proteins VAPA\/B interact with multiple autophagy proteins to modulate autophagosome biogenesis","volume":"28","author":"Zhao","year":"2018","journal-title":"Curr. Biol."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052810\/3702214\/dmm052810.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052810\/3709626\/dmm052810.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052810\/3709626\/dmm052810.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:54:39Z","timestamp":1784894079000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/19\/7\/dmm052810\/372336\/Fos-regulates-age-dependent-neuroinflammation-in-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":112,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.052810","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"dmm052810"}}