The role of membrane trafficking and retromer complex in Parkinson's and Alzheimer's disease

Abstract

Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking. In humans, any interference in normal membrane trafficking or retromer complex can cause profound changes such as those seen in neurodegenerative disorders such as Alzheimer's and Parkinson's. Several studies have explored the potential causative mechanisms in developing both disease processes; however, the role of retromer trafficking in their pathogenesis is becoming increasingly significant with promising therapeutic applications. This manuscript describes the processes involved in membrane transport and the roles of the retromer in the onset and progression of Alzheimer's and Parkinson's. Moreover, we will also explore how these aberrant mechanisms may serve as possible avenues for treatment development in both diseases and the prospect of its future application.

Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations

“…Based on the significance of mutated genes in causing inherited PD, the relevance of these interconnected compartments involved in cell clearance emerged in sporadic PD. These compartments include autophagosomes [36,38,[43][44][45][46][47], proteasome [34,48], endosomes [49,50], retromers [51,52], lysosomes [53][54][55][56][57], mitochondrial turnover [39,[58][59][60][61], and primary protein misfolding [62][63][64].…”