The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy.

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins (receptors, cytokines, enzymes), and may be involved in the pathogenesis of CIPN. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo (HSPs, 20S proteasomes, miRNAs).