323-CCKBR Gq偏向激动剂治疗阿尔茨海默病

这篇文章主要论述了通过靶向胆囊收缩素 B 受体 (CCKBR) 开发针对阿尔茨海默病 (AD) 的选择性信号通路治疗方法。临床证据表明，受损的 CCKBR-Gq 信号传导与 AD 疾病严重程度增加相关，确认了该特定通路具有保护作用。研究人员利用 CCKBR 与不同 G 蛋白结合的冷冻电镜结构，阐明了信号偏向性的分子基础。基于这些结构洞见，他们合理设计出合成激动剂，其中 Gq 偏向性化合物 3r1 在 AD 小鼠模型中展现出治疗潜力。3r1 显著改善了小鼠的认知功能，减少了淀粉样斑块的数量并降低了 p-Tau 蛋白水平。这种益处是通过激活保护性的 CCKBR-Gq-PLCB4-ADAM10 信号通路实现的。References:* Wang J L, Sha X Y, Shao Y, et al. Elucidating pathway-selective biased CCKBR...去小宇宙查看完整单集简介前往小宇宙评论区与主播互动

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