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

FEBS J. 2021 Dec;288(23):6593-6602. doi: 10.1111/febs.15674. Epub 2020 Dec 29.


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

Keywords: Parkinson's disease; cell-to-cell transmission; receptor-mediated endocytosis; unconventional protein secretion; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Exosomes / metabolism
  • Humans
  • Lewy Bodies / metabolism*
  • Microglia / cytology
  • Microglia / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Protein Transport
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein