biostudies-literatureTendulkar SScience and Engineering BoardNHGRI NIH HHSIndian Institute of Science Education and ResearchAgharkar Research InstituteCouncil for Scientific and Industrial ResearchNIGMS NIH HHSNIH HHS2857-2875https://www.ebi.ac.uk/biostudies/studies/S-EPMC9433731biostudies-literatureUnknown31(17)Amyotrophic lateral sclerosis (ALS) is a fatal, late-onset, progressive motor neurodegenerative disorder. A key pathological feature of the disease is the presence of heavily ubiquitinated protein inclusions. Both the unfolded protein response and the ubiquitin-proteasome system appear significantly impaired in patients and animal models of ALS. We have studied cellular and molecular mechanisms involved in ALS using a vesicle-associated membrane protein-associated protein B (VAPB/ALS8) Drosophila model [Moustaqim-Barrette, A., Lin, Y.Q., Pradhan, S., Neely, G.G., Bellen, H.J. and Tsuda, H. (2014) The ALS 8 protein, VAP, is required for ER protein quality control. Hum. Mol. Genet., 23, 1975-1989], which mimics many systemic aspects of the human disease. Here, we show that VAPB, located on tHuman molecular geneticsCaspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease.PMC9433731U41 HG000739P40 OD010949R01 GM084947P40 OD018537Thulasidharan ATendulkar SRatnaparkhi ARatnaparkhi GSHegde SKaduskar BGarg LfalseCaspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease.Amyotrophic lateral sclerosis (ALS) is a fatal, late-onset, progressive motor neurodegenerative disorder. A key pathological feature of the disease is the presence of heavily ubiquitinated protein inclusions. Both the unfolded protein response and the ubiquitin-proteasome system appear significantly impaired in patients and animal models of ALS. We have studied cellular and molecular mechanisms involved in ALS using a vesicle-associated membrane protein-associated protein B (VAPB/ALS8) Drosophila model [Moustaqim-Barrette, A., Lin, Y.Q., Pradhan, S., Neely, G.G., Bellen, H.J. and Tsuda, H. (2014) The ALS 8 protein, VAP, is required for ER protein quality control. Hum. Mol. Genet., 23, 1975-1989], which mimics many systemic aspects of the human disease. Here, we show that VAPB, located on t2022-01-01T00:00:00Z2022 Aug2025-04-04T21:35:17.37Z2024-11-10T06:30:29.572ZS-EPMC94337313537745310.1093/hmg/ddac076