Extracellular Vesicles in Neurodegenerative Diseases: A New Frontier in Diagnosis and Therapy

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the progressive disorders of the nervous system that are characterized by the gradual destruction of neurons, the accumulation of misfolded proteins, and the limited effective therapeutic options. In recent years, numerous lines of evidence have emphasized the important role of extracellular vesicles (EVs) in the formation and progression of these diseases. These vesicles are membrane-bound nanoscale structures that are secreted by almost all cell types and play a role in cell-cell communication through the transfer of molecules such as proteins, lipids, and nucleic acids. In neurodegenerative disorders, EVs can facilitate the transport and dissemination of disease-related proteins, including amyloid-β, tau, α-synuclein, mutant huntingtin, SOD1, and TDP-43, thus contributing to the spread of pathological processes in different parts of the nervous system. On the other hand, the ability of these vesicles to cross the blood-brain barrier and reflect molecular changes occurring in the central nervous system makes them valuable candidates for the development of minimally invasive biomarkers. This review reviews the biogenesis, classification, isolation methods, and molecular content of EVs, and analyzes their role in the pathogenesis, diagnosis, and treatment of the most important neurodegenerative diseases. Also, the importance of EV-associated proteins, RNAs, and lipids as emerging diagnostic biomarkers, as well as the therapeutic potential of natural and engineered vesicles as drug delivery systems and regulators of neuroinflammation and neurodegenerative processes, is discussed.