Dysregulation of Rab5-mediated endocytic pathways in Alzheimer's disease.

Increasing evidence has pointed to that dysregulation of the endo-lysosomal system is an early cellular phenotype of pathogenesis for Alzheimer’s disease (AD). Rab5, a small GTPase, plays a critical role in mediating these processes. Abnormal overactivation of Rab5 has been observed in post-mortem brain samples of Alzheimer’s patients as well as brain samples of mouse models of AD. Recent genome-wide association studies of Alzheimer’s disease have identified RIN3 (Ras and Rab Interactor 3) as a novel risk factor for the disease. RIN3 that functions as a guanine nucleotide exchange factor for Rab5 may serve as an important activator for Rab5 in AD pathogenesis. In the review, we present recent research highlights on the possible roles of dysregulation of Rab5-mediated endocytic pathways in contributing to early pathogenesis of Alzheimer’s disease.

越来越多的证据表明，内溶酶体系统失调是阿尔茨海默病（AD）发病机制的早期细胞表型。Rab5是一种小GTP酶，在介导这些过程中起着关键作用。在阿尔茨海默病患者的死后脑样本以及阿尔茨海默病小鼠模型的脑样本中都观察到了Rab5的异常过度激活。最近对阿尔茨海默病的全基因组关联研究已将RIN3（Ras和Rab相互作用因子3）确定为该疾病的一个新的风险因素。作为Rab5的鸟嘌呤核苷酸交换因子发挥作用的RIN3可能在阿尔茨海默病发病机制中作为Rab5的一个重要激活因子。在这篇综述中，我们介绍了关于Rab5介导的内吞途径失调在促进阿尔茨海默病早期发病机制中可能作用的近期研究重点。