Potential of extracellular vesicles in the Parkinson's disease – Pathological mediators and biomarkers

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the progressive deterioration of motor function. Histopathologically, it is widely accepted that the progressive death of selected dopaminergic neuronal populations and the accumulation of hallmark Lewy bodies (LBs) composed of α-synuclein (α-syn) might be the two vital pathogenesis. Extracellular vesicles (EVs) are cell-derived membranous vesicles that are liberated from virtually all cell types including neurons, and harbor a variety of proteins, DNA, mRNA, and lipids. The roles of these vesicles include cell-cell signaling, removal of unwanted proteins, and transfer of pathogens (including misfolded proteins) between cells. In PD, EVs not only enhance the spread of α-syn at distant sites and reduce their clearance but also mediate other PD pathogenesis such as the activation of microglia and the dysfunction of autophagy and lysosomal degradation systems. Recently, clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers, has merged. In this regard, we reviewed the recent understanding of the biological roles of EVs as important tools for biomarker discovery and pathological regulators of PD, and discuss the main concerns and challenges for the application of EV biomarkers in the clinical setting.