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Identification of the amino acid sequence motif of alpha-synuclein responsible for macrophage activation.

Authors
Lee, SB | Park, SM  | Ahn, KJ | Chung, KC | Paik, SR | Kim, J
Citation
Biochemical and biophysical research communications, 381(1). : 39-43, 2009
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
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.
MeSH

DOI
10.1016/j.bbrc.2009.02.002
PMID
19351591
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
박, 상면
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