화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.331, No.1, 309-317, 2005
Phosphorylated I kappa B alpha is a component of Lewy body of Parkinson's disease
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 Iκ Bα (pIκ Bα), an inhibitor of NF-κ B, and SCFβ-TrCP, the ubiquitin ligase Of pIκ Bα, are components of LB in brains of PD patients. In vitro studies identified those proteins in the ubiquitin- and α-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, Iκ Bα migration into such ubiquitinated inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide known to block phosphorylation of Iκ Bα, although this peptide did not influence cell viability under proteasomal inhibition. Our results indicate that phosphorylation of Iκ Bα plays a role in the formation of Iκ Bα-containing inclusions caused by proteasomal dysfunction, and that the generation of such inclusion is independent of cell death caused by impairment of proteasome. © 2005 Elsevier Inc. All rights reserved.