α-Synuclein-carrying extracellular vesicles in Parkinson's disease: deadly transmitters

Exosomes play a key role in delivery of various biological material and complex signals from one cell to another at long distances. These small extracellular vehicles are involved in mediating multiple physiological and pathogenic processes. In neurodegenerative diseases such as Parkinson's disease (PD), exosomes contribute to disease propagation through transferring misfolded proteins from affected cells to normal cells. In PD, progressive degeneration of neurons arises from the extensive accumulation of toxic forms of alpha-synuclein in the cytoplasm. alpha-Synuclein could exist in several forms, some of which (i.e., oligomeric and polymeric forms) are cytotoxic. Neuron-derived exosomes were found to transfer alpha-synuclein toxic forms between neuronal and non-neuronal cells (such as astrocytes and microglia) thereby contributing to PD spreading. Deposition of alpha-synuclein in glial cells induces inflammation that could be further propagated to other glial cells and neurons. Neuroinflammation promotes degeneration of neurons and aggravates the pathogenesis of PD.