Alpha-synuclein-immunoreactive deposits in human and animal prion diseases.
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 alpha-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). alpha-Synuclein accumulated close to PrPsc deposits but we did not observe strict colocalization of prion protein and alpha-synuclein immunoreactivities particularly in PrPsc plaques. alpha-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 alpha-synuclein in regulating PrPsc formation.
Haïk
S
S
Raymond Escourolle Neuropathology Laboratory, Association Claude Bernard, INSERM U 360, Pitié-Salpêtrière Hospital, 47 Bd. de l'Hôpital, 75013 Paris, France. haik@mailhost.chups.jussieu.fr
Privat
N
N
Adjou
K T
KT
Sazdovitch
V
V
Dormont
D
D
Duyckaerts
C
C
Hauw
J J
JJ
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006224:Cricetinae; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019581:Neuropil / Q000378:metabolism* / Q000473:pathology; D018620:PrPSc Proteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D018620:PrPSc Proteins; D011328:Prions; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein