p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson's disease.
We examined the immunohistochemical localization of p35nck5a, the regulatory subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from patients with Parkinson's disease (PD) and controls. We found p35nck5a immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and neocortex of brains from patients with PD. In addition, p35nck5a 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 p35nck5a regulates the catalytic activity of cdk5 by forming a heterodimer with cdk5, the present results strongly support the hypothesis that a cdk5-p35nck5a complex is involved in the formation of LB fibrils.
Nakamura
S
S
Department of Neurology, Faculty of Medicine, Kyoto University, Japan. i51683@sakura.kudpc.kyoto-u.ac.jp
Kawamoto
Y
Y
Nakano
S
S
Akiguchi
I
I
Kimura
J
J
D000368:Aged; D001369:Axons / Q000737:chemistry; D015153:Blotting, Western; D001921:Brain / Q000648:ultrastructure*; D001923:Brain Chemistry; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000737:chemistry* / Q000201:enzymology*; D008125:Locus Coeruleus / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000276:immunology; D010300:Parkinson Disease / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D013194:Staining and Labeling
D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases