p35^nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson’s disease

Abstract

We examined the immunohistochemical localization of p35^nck5a, the regulatory subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from patients with Parkinson’s disease (PD) and controls. We found p35^nck5a immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and neocortex of brains from patients with PD. In addition, p35^nck5a was colocalized with cdk5 immunoreactivity in LB. Cdk5 is the kinase most likely to be responsible for the phosphorylation of neurofilament proteins of LB, which is a crucial step for the formation of the insoluble LB fibrils. Since p35^nck5a regulates the catalytic activity of cdk5 by forming a heterodimer with cdk5, the present results strongly support the hypothesis that a cdk5-p35^nck5a complex is involved in the formation of LB fibrils.