Cargo trafficking in Alzheimer's disease: the possible role of retromer

Abstract

Alzheimer's disease (AD) as one of the ongoing neurological disorders is initiated and progressed by multiple pathological pathways. Cargoes trafficking pathways, such as recycling, play a crucial role in the pathogenesis of AD. One of the major constituents of this trafficking system in neurons is retromer which acts in endosomal sorting machinery. Defective retromer disrupts recycling of cargoes from endosomes to Golgi and leads to its mis-trafficking which may subsequently leads to AD. Also, retromer-related cargo trafficking could trigger amyloidogenic pathway and beta-amyloid production. Wingless is another cargo in Wnt pathways and its trafficking is mediated by retromer. Retromer malfunction leads to lack of Wnt and subsequent AD-related pathogenesis. Also, retromer plays role in synaptic receptor trafficking in physiologic and pathologic conditions. This review is brief survey on the recent published literatures about pathogenesis of retromer-related trafficking in amyloid precursor protein pathways, Wnt signaling, synaptic function, and also revised the structural role of retromer in AD progression. é 2015, Springer-Verlag Italia.