The reporter learned from the School of Pharmacy at Tsinghua University that Ding Sheng's team recently revealed for the first time the key mechanism that limits the overactivation of microglia, and successfully screened chemical small molecules from over 2400 compounds that can accurately repair this mechanism. In animal experiments, this novel CDK2 inhibitor reduced brain inflammation and restored social and memory functions to normal in diseased mice. This discovery provides a new example for the academic community to deeply understand the regulation of non dividing cell functions by cell cycle proteins, and is also expected to provide a new pathway for the treatment of more than 10 neuroinflammatory related diseases. The microglia in the brain are responsible for clearing metabolic waste, repairing minor injuries, and maintaining the smooth operation of the neural network on a daily basis Ding Sheng introduced, "But when the core component - MEF2C gene - malfunctions, the original protective mechanism will fall into chaos, and neuroinflammation will occur in the brain, which is an important cause of brain diseases such as autism and Alzheimer's disease." To prevent this cellular level "chaos", the research team has built a unique drug screening platform: using fluorescent labeling of cell states and combined with artificial intelligence analysis, 2404 compounds will be carpet scanned. After multiple rounds of screening, a small molecule with the code name BMS265246 stood out. This molecule is like a specially crafted key Ding Sheng explained, "It can precisely insert into the active pocket of CDK2 kinase, and the regulation of this mechanism does not comprehensively suppress the immune system like traditional anti-inflammatory drugs, so it will not affect other normal cell functions." In cell experiments, BMS265246 restored the levels of inflammatory factors to normal within 12 hours without showing cytotoxicity. The research team has cultivated MEF2C deficient mice with autism like symptoms, which not only exhibit severe social impairments but also frequently lose direction in water maze tests. After 8 weeks of treatment with BMS265246, the inflammatory cytokine storm in the brains of this group of autistic mice subsided, and they began actively sniffing their peers, significantly improving their speed in finding the water maze platform. The experiment showed that the drug did not cause weight loss, hair loss, hematological toxicity, or other damage to mice. Ding Sheng introduced that this study not only deepens the understanding of the immune regulation mechanism of microglia, but also provides scientific basis for the development of precise treatment strategies for neuroinflammatory related diseases in the future. (New Society)