Institute of Neurology and Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurosciences, University of California, San Diego, San Diego, California.
Traffic. 2018 Apr;19(4):253-262. doi: 10.1111/tra.12547. Epub 2018 Feb 5.
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 AD 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 this review, we present recent research highlights on the possible roles of dysregulation of Rab5-mediated endocytic pathways in contributing to early pathogenesis of AD.
越来越多的证据表明，内溶酶体系统的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 GTPase，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组织样本以及 AD 小鼠模型的脑组织样本中，均观察到 Rab5 的异常过度激活。最近对 AD 的全基因组关联研究发现 RIN3（Ras 和 Rab 相互作用蛋白 3）是该疾病的一个新的风险因素。RIN3 作为 Rab5 的鸟嘌呤核苷酸交换因子，可能在 AD 的发病机制中作为 Rab5 的重要激活剂。在这篇综述中，我们介绍了最近关于 Rab5 介导的内吞途径失调在 AD 早期发病机制中作用的研究要点。
