Identification of the amino acid sequence motif of alpha-synuclein responsible for macrophage activation.
Biochem Biophys Res Commun
; 381(1): 39-43, 2009 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-19351591
ABSTRACT
Alpha-synuclein (Syn) is implicated in the pathogenesis of PD and related neurodegenerative disorders. Recent studies have also shown that alpha-synuclein can activate microglia and enhance dopaminergic neurodegeneration. The mechanisms of microglia activation by alpha-synuclein, however, are not well understood. In this study, we found that not only alpha-synuclein but also beta- and gamma-synucleins activated macrophages (RAW 264.7) in vitro. Macrophages treated with synuclein proteins secreted TNF-alpha in a dose-dependent manner. Synuclein family proteins also increased mRNA transcription of COX-2 and iNOS. Two alpha-synuclein deletion mutants, SynDeltaNAC and Syn61-140, activated macrophages, while deletion mutants Syn1-60 and Syn96-140 did not significantly activate them. Finally, we demonstrated that macrophage activation by alpha-synuclein was accompanied by phosphorylation of ERK. These results suggest that synuclein family proteins can activate macrophages, and that macrophage activation needs both the N-terminal and C-terminal domains of alpha-synuclein, but not the central NAC region.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alfa-Sinucleína
/
Ativação de Macrófagos
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Macrófagos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2009
Tipo de documento:
Article