Extracellular vesicle-associated small heat shock proteins as therapeutic agents in neurodegenerative diseases and beyond

[Display omitted] Increasing evidence points towards using extracellular vesicles (EVs) as a therapeutic strategy in neurodegenerative diseases such as multiple sclerosis, Parkinson’s, and Alzheimer’s disease. EVs are nanosized carriers that play an essential role in intercellular communication and cellular homeostasis by transporting an active molecular cargo, including a large variety of proteins. Recent publications demonstrate that small heat shock proteins (HSPBs) exhibit a beneficial role in neurodegenerative diseases. Moreover, it is defined that HSPBs target the autophagy and the apoptosis pathway, playing a prominent role in chaperone activity and cell survival. This review elaborates on the therapeutic potential of EVs and HSPBs, in particular HSPB1 and HSPB8, in neurodegenerative diseases. We conclude that EVs and HSPBs positively influence neuroinflammation, central nervous system (CNS) repair, and protein aggregation in CNS disorders. Moreover, we propose the use of HSPB-loaded EVs as advanced nanocarriers for the future development of neurodegenerative disease therapies.