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

Authors
 Saet-byul Lee  ;  Sang Myun Park  ;  Keun Jae Ahn  ;  Kwang Chul Chung  ;  Seung R. Paik  ;  Jongsun Kim 
Citation
 Biochemical and Biophysical Research Communications, Vol.381(1) : 39-43, 2009 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2009
MeSH
Amino Acid Motifs/genetics ; Animals ; Cell Line ; DNA Mutational Analysis ; Humans ; Macrophage Activation*/genetics ; Macrophages/drug effects ; Macrophages/immunology* ; Mice ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Sequence Analysis, Protein ; Sequence Deletion ; alpha-Synuclein/genetics ; alpha-Synuclein/pharmacology ; alpha-Synuclein/physiology*
Keywords
Synuclein ; TNF-α ; Macrophage ; Inflammation ; Parkinson’s disease
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X09002460
DOI
10.1016/j.bbrc.2009.02.002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
Park, Sang Myun(박상면)
Ahn, Keun Jae(안근재)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103483
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