Genes associated with amyloid-beta-induced inflammasome-mediated neuronal death identified using functional gene trap mutagenesis approach

Alzheimer’s disease is an irreversible neurodegenerative disease, which accounts for most dementia cases. Neuroinflammation increasingly recognised its roles in pathogenesis which, part, links amyloid-beta to neuronal death. Neuroinflammatory signalling can be exhibited by neurons themselves, potentially leading widespread cell death, although neuroinflammation commonly associated with glial cells. The presence of the inflammasomes such as nucleotide-binding leucine-rich repeat receptors protein 1 accelerates -induced and has been shown trigger pyroptosis murine models. However, pathways involved activation have yet elucidated. In this study, a gene trap mutagenesis approach was utilised resolve genes functionally inflammasome within neurons, mechanism behind amyloid-beta-induced results indicate that significantly accelerated neuroinflammatory death primed (the NLR family pyrin domain-containing 1). screen discovered atypical mitochondrial Ras homolog member T1 significant contributor -mediated also identified two transforming growth factor beta signalling, namely Transforming Growth Factor Beta Receptor SNW domain containing 1. Additionally, cytoskeletal reorganisation, SLIT-ROBO Rho GTPase Activating Protein 3 found neuroprotective. conclusion, these could play important makes them promising therapeutic targets future drug development against disease.