抄録
Cyclin-dependent serine/threonine protein kinases (CDK) are regulated by activating protein called cyclin. CDKs play physiological roles in regulating cell cycle progression. CDK5, unlike other CDKs, is active only in post-mitotic neurons in the CNS. Recently, CDK5 and its activators are suspected to be a risk factor of Alzheimer's disease (AD). Truncation of p35, a CDK5 activator, into p25 modulates CDK5 activity, and produces an intensive phosphorylation at Ser202 and Thr205 of tau protein. We hypothesize that phosphorylation of these closely-packed sites induces conformation change of tau that allows access of a wider variety of tau kinases to the possible phosphorylation sites located in the assembly domain. The resulting hyperphosphorylation of tau could play a pivotal role in the pathogenesis of AD. If so, an inhibition of CDK5 may effectively rescue neuronal cell death in AD patients brain. We have set off a search for CDK-antagonizing flavonoids using water-dispersible propolis (WDP), and found that WDP inhibited cell-growth of rat C6 glioma cell line at a reasonable concentration. The result also demonstrates that WDP, unlike the ethanol extract of propolis, is suitable for in-vitro experiments. [Jpn J Physiol 55 Suppl:S204 (2005)]
