Seeded propagation of α-synuclein aggregation in mouse brain using protein misfolding cyclic amplification.
PMCA
prion
seeding
α-syn
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
pubmed:
3
8
2019
medline:
9
6
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
α-Synuclein (α-syn) protein aggregation is associated with several neurodegenerative disorders collectively referred to as synucleinopathies, including Parkinson's disease. We used protein misfolding cyclic amplification (PMCA) to study α-syn aggregation in brain homogenates of wild-type or transgenic mice expressing normal (D line) or A53T mutant (M83 line) human α-syn. We found that sonication-incubation cycles of M83 mouse brain gradually produce large quantities of SDS-resistant α-syn aggregates, involving both human and mouse proteins. These PMCA products, containing partially proteinase K-resistant α-syn species, are competent to accelerate the onset of neurologic symptoms after intracerebral inoculation to young M83 mice and to seed aggregate formation of α-syn following PMCA, including in D and wild-type mouse brain substrates. PMCA seeding activity in the M83 diseased brain correlates positively with regions mostly targeted by the α-syn pathology in this model. Our data indicate that similar to prions, PMCA can reproduce some characteristics of α-syn aggregation and seeded propagation
Identifiants
pubmed: 31370680
doi: 10.1096/fj.201900354R
pmc: PMC6902716
doi:
Substances chimiques
Protein Aggregates
0
alpha-Synuclein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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