Neuroprotective Effects of Huperzine A
Wang R. · Tang X.C.
A Natural Cholinesterase Inhibitor for the Treatment of Alzheimer’s Disease
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, China
Prof. Xi Can Tang, State Key Laboratory of Drug Research
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences
Chinese Academy of Sciences, 555 Zu Chong Zhi Road
Zhangjiang Hi-Tech Park, Shanghai 201203 (China)
Tel. +86 21 5080 6710, Fax +86 21 5080 7088, E-Mail email@example.com
Keywords: Huperzine AAlzheimer’s diseaseAcetylcholinesteraseCholinesterase inhibitorCognitive enhancerNeuroprotectionOxidative stressBeta-amyloidAmyloid precursor proteinCerebral ischemiaApoptosisApoptotic-related geneMitochondriaGlutamateNMDA receptorPotassium current
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Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase. It has been found to reverse or attenuate cognitive deficits in a broad range of animal models. Clinical trials in China have demonstrated that HupA significantly relieves memory deficits in aged subjects, patients with benign senescent forgetfulness, Alzheimer’s disease (AD) and vascular dementia (VD), with minimal peripheral cholinergic side effects compared with other AChEIs in use. HupA possesses the ability to protect cells against hydrogen peroxide, β-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53 and caspase-3, protect mitochondria, and interfere with APP metabolism. Antagonizing effects on NMDA receptors and potassium currents may contribute to the neuroprotection as well. It is also possible that the non-catalytic function of AChE is involved in neuroprotective effects of HupA. The therapeutic effects of HupA on AD or VD are probably exerted via a multi-target mechanism.
© 2005 S. Karger AG, Basel
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