α-synuclein strains that cause distinct pathologies differentially inhibit proteasome.
mouse
neuroscience
prion
proteasome
strain
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
22 07 2020
22 07 2020
Historique:
received:
11
03
2020
accepted:
22
07
2020
pubmed:
23
7
2020
medline:
13
2
2021
entrez:
23
7
2020
Statut:
epublish
Résumé
Abnormal α-synuclein aggregation has been implicated in several diseases and is known to spread in a prion-like manner. There is a relationship between protein aggregate structure (strain) and clinical phenotype in prion diseases, however, whether differences in the strains of α-synuclein aggregates account for the different pathologies remained unclear. Here, we generated two types of α-synuclein fibrils from identical monomer and investigated their seeding and propagation ability in mice and primary-cultured neurons. One α-synuclein fibril induced marked accumulation of phosphorylated α-synuclein and ubiquitinated protein aggregates, while the other did not, indicating the formation of α-synuclein two strains. Notably, the former α-synuclein strain inhibited proteasome activity and co-precipitated with 26S proteasome complex. Further examination indicated that structural differences in the C-terminal region of α-synuclein strains lead to different effects on proteasome activity. These results provide a possible molecular mechanism to account for the different pathologies induced by different α-synuclein strains.
Identifiants
pubmed: 32697196
doi: 10.7554/eLife.56825
pii: 56825
pmc: PMC7406352
doi:
pii:
Substances chimiques
Fungal Proteins
0
alpha-Synuclein
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
ATP dependent 26S protease
EC 3.4.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 16K21650
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science, and Technology
ID : 26117005
Pays : International
Organisme : Core Research for Evolutional Science and Technology
ID : JPMJCR18H3
Pays : International
Organisme : Japan Agency for Medical Research and Development
ID : JP18dm0207019
Pays : International
Informations de copyright
© 2020, Suzuki et al.
Déclaration de conflit d'intérêts
GS, SI, MH, RK, TN, SH, YS, MH No competing interests declared
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