The Role of Retromer in Alzheimer's Disease.

ABSTRACT

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)/ß-site APP-cleaving enzyme 1 (BACE1) away endosomes that reduces the production of amyloid ß (Aß). And, tetramer is also found to regulate phagocytic receptors to the plasma membrane of microglia, where some phagocytic receptors take part in Aß clearance. Therefore, disruption of retromer will increase the production of Aß. 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.