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

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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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Acknowledgments

We thank Drs Khalid Iqbal and Inge Grundke-Iqbal from NYS Institute for Basic Research for support of reagents and scientific discussions. We thank Dr Cheng-Xin Gong from the same institute for prove-reading of the paper. This work was supported in part by grants from the Natural Science Foundation of China (30430270, 30472030 and 30400068), and the Science and Technology Committee of China (2006CB500703).

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Authors and Affiliations

  1. Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R. China

    Shaohui Wang, Lingqiang Zhu, Hairong Shi, Hongyun Zheng, Qing Tian, Qun Wang, Rong Liu & Jian-Zhi Wang

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  1. Shaohui Wang
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  2. Lingqiang Zhu
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  3. Hairong Shi
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  4. Hongyun Zheng
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  5. Qing Tian
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  6. Qun Wang
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  7. Rong Liu
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  8. Jian-Zhi Wang
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Correspondence to Jian-Zhi Wang.

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S. Wang and L. Zhu contributed equally to this paper.

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Wang, S., Zhu, L., Shi, H. et al. Inhibition of Melatonin Biosynthesis Induces Neurofilament Hyperphosphorylation with Activation of Cyclin-dependent Kinase 5. Neurochem Res 32, 1329–1335 (2007). https://doi.org/10.1007/s11064-007-9308-y

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  • DOI: https://doi.org/10.1007/s11064-007-9308-y

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