袁钧瑛院士团队最新Immunity：提出阿尔茨海默病治疗新策略

Core Viewpoint - The study highlights the role of INPP5D in inhibiting RIPK1 kinase, which is linked to the expression of pro-inflammatory mediators and risk factors for late-onset Alzheimer's disease (LOAD) [4][9]. Group 1: Research Findings - INPP5D directly interacts with RIPK1 at the p-Y383 site, inhibiting its activation, which is crucial for regulating inflammation and LOAD risk gene transcription in microglia [6][7]. - The loss of INPP5D in microglia promotes RIPK1-mediated transcription of various LOAD risk genes and pro-inflammatory cytokines, leading to neurodegenerative changes [6][7]. - The study identifies RIPK1 activation markers in lipid-handling microglial subtypes associated with human Alzheimer's disease [7]. Group 2: Implications for Treatment - Restoring or enhancing INPP5D function may represent a potential new strategy for treating late-onset Alzheimer's disease [4][9]. - The research suggests that INPP5D acts as an intracellular regulator of RIPK1-mediated neuroinflammation, contributing to age-related neurodegenerative diseases, including LOAD and Alzheimer's disease with amyotrophic lateral sclerosis (AD-ALS) comorbidity [9].