{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333178/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Drosophila melanogaster"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333178"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Fos regulates age-dependent neuroinflammation in VAPBALS","description":"Amyotrophic 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.","dates":{"publication":"2026/06/27"},"accession":"GSE333178","cross_references":{"GSM":["GSM9758492","GSM9758491","GSM9758490","GSM9758496","GSM9758495","GSM9758494","GSM9758493","GSM9758539","GSM9758538","GSM9758533","GSM9758499","GSM9758532","GSM9758531","GSM9758498","GSM9758497","GSM9758530","GSM9758537","GSM9758536","GSM9758535","GSM9758534","GSM9758481","GSM9758480","GSM9758485","GSM9758484","GSM9758483","GSM9758482","GSM9758529","GSM9758528","GSM9758527","GSM9758522","GSM9758489","GSM9758488","GSM9758521","GSM9758520","GSM9758487","GSM9758486","GSM9758526","GSM9758525","GSM9758524","GSM9758523","GSM9758470","GSM9758474","GSM9758473","GSM9758472","GSM9758471","GSM9758519","GSM9758518","GSM9758517","GSM9758516","GSM9758511","GSM9758478","GSM9758477","GSM9758510","GSM9758476","GSM9758475","GSM9758515","GSM9758514","GSM9758513","GSM9758479","GSM9758512","GSM9758540","GSM9758463","GSM9758462","GSM9758508","GSM9758507","GSM9758506","GSM9758505","GSM9758549","GSM9758509","GSM9758500","GSM9758544","GSM9758467","GSM9758543","GSM9758466","GSM9758542","GSM9758465","GSM9758464","GSM9758541","GSM9758548","GSM9758504","GSM9758503","GSM9758547","GSM9758502","GSM9758546","GSM9758469","GSM9758545","GSM9758468","GSM9758501"],"GPL":["34457","22106"],"GSE":["333178"],"taxon":["Drosophila melanogaster"]}}