GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333178/primary200OKTranscriptomicsDrosophila melanogasterExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333178GEOGSEfalseFos regulates age-dependent neuroinflammation in VAPBALSAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor function. We have developed a Drosophila model of ALS8 (VAPBP58S) using CRISPR/Cas9 genome editing. VAPB is an ER-based adapter protein associated with and regulating intracellular membrane:membrane contact sites. VAPBP58S flies show progressive age-dependent motor deficits and a shortened lifespan, paralleling features of the human disease. VAPBP58S brains exhibit age-dependent neuroinflammation, as measured by whole-transcriptome quantitative mRNA sequencing, suggesting a broad, low-grade enhancement in signalling in multiple (Toll, IMD, Jak-STAT and Jun-kinase) immune pathways. We implicate glial cells in the brain as the site of brain inflammation and identify Drosophila Fos (Kayak) as a key modulator of age-dependent inflammation. In accordance, we find that overexpression of wild-type kayak or its dominant-active variant kayakK357R in glia reduces inflammation and, concomitantly, improves motor function. In contrast, knockdown of glial kayak accelerates age-dependent deterioration of motor function and enhances 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.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 melanogaster