Nature Aging：王宏林团队发现阿尔茨海默病治疗新靶点，并找到潜在药物

Core Insights - The study highlights the role of lipid metabolism dysregulation in promoting chronic microglial activation and neuroinflammation in Alzheimer's disease (AD) [2][6] - MFE-2 is identified as a potential drug target, with the small molecule CKBA showing promise in restoring MFE-2 expression and treating AD [6] Group 1: Research Findings - The expression level of MFE-2, a key enzyme regulating fatty acid β-oxidation, is found to be decreased in microglia from both human AD patients and AD model mice [3] - Specific knockout of MFE-2 in microglia of AD model mice leads to microglial abnormalities, neuroinflammation, and β-amyloid (Aβ) deposition [3] - The absence of MFE-2 promotes lipid accumulation, resulting in excessive arachidonic acid, increased mitochondrial reactive oxygen species (ROS), and production of pro-inflammatory cytokines [3] Group 2: Therapeutic Potential - The natural triterpenoid compound AKBA's derivative CKBA can bind with high affinity to MFE-2, stabilizing its levels and inhibiting excessive microglial activation [3] - CKBA improves neuroinflammation and pathological damage associated with Alzheimer's disease [3][6]