Molecular events underlying the cell-to-cell transmission of alpha-synuclein

The pathogenesis of Parkinson's disease (PD), which is a progressive neurodegenerative disease, is associated with the formation of protein inclusion bodies called Lewy bodies (LB) or Lewy neurites (LN). alpha-Synuclein (alpha-Syn) is a major component of LB and LN. The formation of LB or LN is mediated by formation of alpha-Syn fibrils, which are formed from alpha-Syn monomers and oligomers. Additionally, intercellular alpha-Syn propagation has been proposed to be important for the progression of PD. Thus, various studies have focused on elucidating the role of alpha-Syn propagation in the pathogenesis of PD. Previous studies have reported that alpha-Syn species are released from the cells through various pathways, including the unconventional secretion pathways. The released alpha-Syn species are internalized by the cells through multiple mechanisms, including receptor-mediated endocytosis. Some molecular processes involved in intercellular alpha-Syn propagation have been recently elucidated. This review discusses the current studies on the molecular mechanisms underlying the release and uptake of alpha-Syn and their physiological relevance.