Wang Shaohui, Zhu Lingqiang, Shi Hairong, Zheng Hongyun, Tian Qing, Wang Qun, Liu Rong, Wang Jian-Zhi
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Neurochem Res. 2007 Aug;32(8):1329-35. doi: 10.1007/s11064-007-9308-y. Epub 2007 Mar 31.
Decreased level of melatonin and hyperphosphorylation of neurofilament proteins have been reported in Alzheimer's disease (AD). However, the direct evidence linking melatonin and neurofilament phosphorylation is still lacking. Here, we investigated the effect of inhibiting melatonin biosynthesis on phosphorylation of neurofilament proteins and the involvement of cyclin-dependent kinase 5 (cdk-5) in rats. We observed that injection of haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase, resulted in significantly decreased level of serum melatonin with a concomitantly increased phosphorylation of neurofilament proteins and activation of cdk-5 in rats. Exogenous supplementation of melatonin partially arrested the hyperphosphorylation of neurofilament and the activation of cdk-5. These results suggest that inhibition of melatonin biosynthesis may activate cdk-5 and thus induces Alzheimer-like hyperphosphorylation of neurofilament proteins.
