Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease

Biochem Biophys Res Commun. 2005 May 27;331(1):309-17. doi: 10.1016/j.bbrc.2005.03.167.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • I-kappa B Proteins / analysis
  • I-kappa B Proteins / metabolism*
  • Lewy Bodies / chemistry
  • Lewy Bodies / enzymology*
  • NF-KappaB Inhibitor alpha
  • Parkinson Disease / enzymology*
  • Parkinson Disease / pathology
  • Peptides / pharmacology
  • Phosphorylation
  • Protease Inhibitors / pharmacology
  • Proteasome Inhibitors
  • SKP Cullin F-Box Protein Ligases / analysis
  • Ubiquitin / analysis

Substances

  • I-kappa B Proteins
  • NBD peptide, mouse
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Peptides
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Ubiquitin
  • NF-KappaB Inhibitor alpha
  • SKP Cullin F-Box Protein Ligases