The Role of Exosomes in Lysosomal Storage Disorders

Exosomes, small membrane-bound organelles formed from endosomal membranes, represent a heterogenous source of biological and pathological biomarkers capturing the metabolic status of a cell. Exosomal cargo, including lipids, proteins, mRNAs, and miRNAs, can either act as inter-cellular messengers or are shuttled for autophagic/lysosomal degradation. Most cell types in the central nervous system (CNS) release exosomes, which serve as long and short distance communicators between neurons, astrocytes, oligodendrocytes, and microglia. Lysosomal storage disorders are diseases characterized by the accumulation of partially or undigested cellular waste. The exosomal content in these diseases is intrinsic to each individual disorder. Emerging research indicates that lysosomal dysfunction enhances exocytosis, and hence, in lysosomal disorders, exosomal secretion may play a role in disease pathogenesis. Furthermore, the unique properties of exosomes and their ability to carry cargo between adjacent cells and organs, and across the blood–brain barrier, make them attractive candidates for use as therapeutic delivery vehicles. Thus, understanding exosomal content and function may have utility in the treatment of specific lysosomal storage disorders. Since lysosomal dysfunction and the deficiency of at least one lysosomal enzyme, glucocerebrosidase, is associated with the development of parkinsonism, the study and use of exosomes may contribute to an improved understanding of Parkinson disease, potentially leading to new therapeutics.