Pathogenic Extracellular Vesicle (EV) Signaling in Amyotrophic Lateral Sclerosis (ALS).

Extracellular vesicles (EVs), once considered a pathway for cells to remove waste, have now emerged as an important mechanism for intercellular communication. EVs are particularly appealing in understanding the central nervous system (CNS) communication, given that there are very diverse cell types in the CNS and constant communications among various cells to respond to the frequently changing environment. While they are heterogeneous and new vesicles are continuously to be discovered, EVs are primarily classified as plasma membrane-derived microvesicles (MVs) and endosome-derived exosomes. Secretion of EVs has been shown from all CNS cell types in vitro and intercellular EV signaling has been implicated in neural development, axon integrity, neuron to glia communication, and propagation of protein aggregates formed by disease pathogenic proteins. However, significant hurdles remain to be tackled in understanding their physiological and pathological roles as well as how they can be developed as biomarkers or new therapeutics. Here we provide our summary on the known cell biology of EVs and discuss opportunities and challenges in understanding EV biology in the CNS and particularly their involvement in ALS pathogenesis.