Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation.
J Biol Chem
; 274(14): 9843-6, 1999 Apr 02.
Article
em En
| MEDLINE
| ID: mdl-10092675
ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Fosfoproteínas
/
Mutação
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article