Phosphorylated IκBα 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 IκBα (pIκBα), an inhibitor of NF-κB, and SCFβ-TrCP, the ubiquitin ligase of pIκBα, 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, IκBα migration into such ubiquitinated inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide known to block phosphorylation of IκBα, although this peptide did not influence cell viability under proteasomal inhibition. Our results indicate that phosphorylation of IκBα plays a role in the formation of IκBα-containing inclusions caused by proteasomal dysfunction, and that the generation of such inclusion is independent of cell death caused by impairment of proteasome.