Progress in the pathogenesis of α-synuclein

Deposition of intracellular misfolded α-synuclein (α-syn) in the central nervous system and peripheral nervous system leads to Parkinson′s disease, dementia with Lewy body, multiple system atrophy and other synucleinopathies. But the pathological mechanism of the transmission is not fully understood. Recent studies have shown that intercellular transmission of neurotoxic oligomer α-syn is the main mode of disease transmission between brain regions. This article reviews the existing evidence for different modes of cell secretion and uptake of oligomer α-syn, including direct intercellular transmission, prion-like transmission, exosomes and endocytosis, tunneling nanotubes and microglia-mediated, to provide a more detailed understanding of the patterns of synucleinopathy throughout the brain and to provide new targets for the treatment of disease. Key words: α-Synuclein; Synucleinopathy; Exosomes; Prion-like; Endocytosis; Tunneling nanotubes; Microglia