Document Detail

Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease.
MedLine Citation:
PMID:  15845394     Owner:  NLM     Status:  MEDLINE    
Ubiquitin is one of the major components of Lewy bodies (LB), the pathological hallmark of Parkinson's disease (PD). Here, we identified that a phosphorylated form of IkappaBalpha (pIkappaBalpha), an inhibitor of NF-kappaB, and SCF(beta-TrCP), the ubiquitin ligase of pIkappaBalpha, are components of LB in brains of PD patients. In vitro studies identified those proteins in the ubiquitin- and alpha-synuclein (known as the major component of LB)-positive LB-like inclusions generated in dopaminergic SH-SY5Y cells treated with MG132, a proteasome inhibitor. Intriguingly, IkappaBalpha migration into such ubiquitinated inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide known to block phosphorylation of IkappaBalpha, although this peptide did not influence cell viability under proteasomal inhibition. Our results indicate that phosphorylation of IkappaBalpha plays a role in the formation of IkappaBalpha-containing inclusions caused by proteasomal dysfunction, and that the generation of such inclusion is independent of cell death caused by impairment of proteasome.
Kazuyuki Noda; Toshiaki Kitami; Wei Ping Gai; Fariba Chegini; Poul Henning Jensen; Tsutomu Fujimura; Kimie Murayama; Keiji Tanaka; Yoshikuni Mizuno; Nobutaka Hattori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  331     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-22     Completed Date:  2005-06-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  309-17     Citation Subset:  IM    
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
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MeSH Terms
Cell Line, Tumor
I-kappa B Proteins / analysis,  metabolism*
Lewy Bodies / chemistry,  enzymology*
Parkinson Disease / enzymology*,  pathology
Peptides / pharmacology
Protease Inhibitors / pharmacology
Proteasome Endopeptidase Complex / antagonists & inhibitors
SKP Cullin F-Box Protein Ligases / analysis
Ubiquitin / analysis
Reg. No./Substance:
0/I-kappa B Proteins; 0/NBD peptide, mouse; 0/Peptides; 0/Protease Inhibitors; 0/Ubiquitin; 139874-52-5/NF-kappaB inhibitor alpha; EC Endopeptidase Complex; EC Cullin F-Box Protein Ligases

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