Different α-synuclein prion strains cause dementia with Lewy bodies and multiple system atrophy.
dementia with Lewy bodies
neurodegeneration
prions
strains
synucleinopathies
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
08 02 2022
08 02 2022
Historique:
accepted:
03
12
2021
entrez:
4
2
2022
pubmed:
5
2
2022
medline:
26
2
2022
Statut:
ppublish
Résumé
The α-synuclein protein can adopt several different conformations that cause neurodegeneration. Different α-synuclein conformers cause at least three distinct α-synucleinopathies: multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and Parkinson's disease (PD). In earlier studies, we transmitted MSA to transgenic (Tg) mice and cultured HEK cells both expressing mutant α-synuclein (A53T) but not to cells expressing α-synuclein (E46K). Now, we report that DLB is caused by a strain of α-synuclein prions that is distinct from MSA. Using cultured HEK cells expressing mutant α-synuclein (E46K), we found that DLB prions could be transmitted to these HEK cells. Our results argue that a third strain of α-synuclein prions likely causes PD, but further studies are needed to identify cells and/or Tg mice that express a mutant α-synuclein protein that is permissive for PD prion replication. Our findings suggest that other α-synuclein mutants should give further insights into α-synuclein prion replication, strain formation, and disease pathogenesis, all of which are likely required to discover effective drugs for the treatment of PD as well as the other α-synucleinopathies.
Identifiants
pubmed: 35115402
pii: 2113489119
doi: 10.1073/pnas.2113489119
pmc: PMC8833220
pii:
doi:
Substances chimiques
Prions
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : P01 AG002132
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Informations de copyright
Copyright © 2022 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: S.B.P. is a member of the Scientific Advisory Boards of ViewPoint Therapeutics and New Ventures Inc. and a member of the Supervisory Board of Priavoid, none of which have contributed financial or any other support to these studies.
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