Alpha-synuclein-immunoreactive deposits in human and animal prion diseases

Abstract

Prion related disorders are associated with the accumulation of a misfolded isoform (PrPsc) of the host-encoded prion protein, PrP. There is strong evidence for the involvement of unidentified co-factors in the PrP to PrPsc conversion process. In this study, we show α-synuclein-immunoreactive deposits in the central nervous system of various prion diseases (sporadic, iatrogenic and new variant Creutzfeldt-Jakob diseases, and experimental scrapie of hamsters). α-Synuclein accumulated close to PrPsc deposits but we did not observe strict colocalization of prion protein and α-synuclein immunoreactivities particularly in PrPsc plaques. α-Synuclein is thought to be a key player in some neurodegenerative disorders, is able to interact with amyloid structures and has known chaperone-like activities. Our results, in various prion diseases, suggest a role for α-synuclein in regulating PrPsc formation.