Neurochemical Research

, Volume 36, Issue 5, pp 801–811 | Cite as

RETRACTED ARTICLE: Fuzhisan, a Chinese Herbal Medicine, Inhibits Beta-Amyloid-Induced Neurotoxicity and Tau Phosphorylation Through Calpain/Cdk5 Pathway in Cultured Cortical Neurons

Original Paper
First Online:
Accepted:

Abstract

It has been shown that β-amyloid (Aβ) induced hyperphosphorylation of tau is implicated in the pathogenesis of Alzheimer’s disease (AD), and deregulation of cyclin-dependent kinase 5 (Cdk5) activity is involved in the abnormal tau phosphorylation. The cleavage of neuron-specific Cdk5 activator, p35, to p25, mediated by calpain and calcium, deregulates Cdk5 activity and promotes neurodegeneration. Fuzhisan (FZS), a Chinese herbal complex prescription that has been used for the treatment of AD for over 15 years, is known to enhance the cognitive ability in AD patients. In this study, we investigated the neuroprotective effects and potential molecular mechanisms of FZS against Aβ25–35-induced toxicity in cultured cortical neurons. We revealed that FZS attenuated Aβ25–35-induced neurotoxicity in a dose-dependent manner. FZS inhibited Aβ25–35-induced activation of Cdk5 and decreased tau hyperphosphorylation although it did not directly inhibit Cdk5. In addition, FZS also blocked Aβ25–35-induced calcium influx, calpain activation and decreased cleavage of p35 to p25.

Keywords

Fuzhisan (FZS) Alzheimer’s disease Tau Cyclin-dependent kinase 5 (CDK5) p35 p25 

Abbreviations

AD

Alzheimer’s disease

Aβ

β-amyloid

NFTs

neurofibrillary tangles

GSK3β

Glycogen synthase kinase 3 beta

Cdk5

Cyclin-dependent kinase 5

FZS

Fuzhisan

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Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 30973106) and Natural Science Foundation of HeiLongJiang Province (No.CB08C309).

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Neurologythe First Affiliated Hospital, Harbin Medical UniversityHarbinChina
  2. 2.Department of PathologyThe First Affiliated Hospital, Harbin Medical UniversityHarbinChina

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