Inhibition of Melatonin Biosynthesis Induces Neurofilament Hyperphosphorylation with Activation of Cyclin-dependent Kinase 5

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2007 Apr 3

PMID 17401652

Citations 8

Authors

Shaohui Wang

Lingqiang Zhu

Hairong Shi

Hongyun Zheng

Qing Tian

Qun Wang

Rong Liu

Jian-Zhi Wang

Affiliations

Soon will be listed here.

Abstract

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.

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