Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Mol Neurobiol. 2016 Aug;53(6):4201-4209. doi: 10.1007/s12035-015-9366-0. Epub 2015 Jul 28.
The retromer complex is an important component of the endosomal protein sorting machinery and mediates protein cargoes from endosomes to the trans-Golgi network (TGN) by retrograde pathway or to the cell surface through recycling pathway. Studies show that retromer and its receptors can make amyloid precursor protein (APP)/β-site APP-cleaving enzyme 1 (BACE1) away endosomes that reduces the production of amyloid β (Aβ). And, tetramer is also found to regulate phagocytic receptors to the plasma membrane of microglia, where some phagocytic receptors take part in Aβ clearance. Therefore, disruption of retromer will increase the production of Aβ. Recently, a plausible relationship between disturbance of retromer and tauopathies is raised. Retromer dysfunction may result in decreasing the clearance of extracellular tau and the level of cathepsin D, which enables tau-induced neurotoxicity. This review article summarizes the structure and function of retromer and its role in pathogenesis of AD. In the end, retromer may provide a potential therapeutic strategy for the treatment of AD.
回转体复合物是内体蛋白分选机制的重要组成部分，通过逆行途径将蛋白货物从内体转运到反式高尔基网络（TGN），或者通过再循环途径转运到细胞表面。研究表明，回转体及其受体可以使淀粉样前体蛋白（APP）/β-位点 APP 裂解酶 1（BACE1）离开内体，从而减少淀粉样 β（Aβ）的产生。此外，四聚体还被发现调节小胶质细胞质膜上的吞噬受体，其中一些吞噬受体参与 Aβ 的清除。因此，回转体的破坏会增加 Aβ的产生。最近，提出了回转体紊乱与 tau 病之间可能存在的关系。回转体功能障碍可能导致细胞外 tau 和组织蛋白酶 D 的清除减少，从而导致 tau 诱导的神经毒性。本文综述了回转体的结构和功能及其在 AD 发病机制中的作用。最后，回转体可能为 AD 的治疗提供一种潜在的治疗策略。
