A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders

Extracellular vesicles (EVs) are a heterogeneous population of stable lipid membrane particles that play critical role in the regulation numerous physiological and pathological processes. EV cargo, which includes lipids, proteins, RNAs including miRNAs, is affected by metabolic status parental cell. Concordantly, abnormalities autophagic-endolysosomal pathway, as seen lysosomal storage disorders (LSDs), can affect release well cargo. LSDs group over 70 inheritable diseases, characterized dysfunction gradual accumulation undigested molecules. caused single gene mutations lead to deficiency protein or lipid. Lysosomal sets off cascade alterations endolysosomal pathway autophagy alter calcium homeostasis, leading energy imbalance, oxidative stress, apoptosis. The pathophysiology these diseases very heterogenous, complex, currently incompletely understood. progressive multisystemic symptoms often include neurological deficits. In this review, kaleidoscopic overview will be given on roles EVs LSDs, from their contribution pathology diagnostics drug delivery vehicles. Furthermore, cargo surface engineering strategies discussed show potential future LSD treatment, both context enzyme replacement therapy, editing like CRISPR/Cas. use engineered vehicles may mask therapeutic immune system protect it degradation, improving circulation time targeted delivery.