title: Inhibition of melatonin biosynthesis induces neurofilament hyperphosphorylation with activation of cyclin-dependent kinase 5.
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.
authors.affiliation: Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Wang
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhu
authors.forename: Hairong
authors.initials: H
authors.lastname: Shi
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D004789:Enzyme Activation; D006220:Haloperidol / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D008550:Melatonin / Q000096:biosynthesis* / Q000097:blood; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018492:Dopamine Antagonists; D016900:Neurofilament Proteins; D051360:Cyclin-Dependent Kinase 5; D006220:Haloperidol; D008550:Melatonin