Neuroprotective Effects of Huperzine A

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, ß-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. Copyright © 2005 S. Karger AG, Basel Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder associated with a global impairment of higher mental function, and presenting an impairment of memory as the cardinal symptom [1]. Histopathological hallmarks of the disease are the extracellular deposition of amyloid ß-peptide (Aß) in senile plaques, the appearance of intracellular neurofibrillary tangles (NFT), a loss of cholinergic neurons, and extensive synaptic changes in the cerebral cortex, hippocampus and other areas of brain essential for cognitive functions. To date, the cause and the mechanism by which neurons die in AD remain unclear, but Aß has been established as a crucial factor in AD pathogenesis. Aß deposition may cause neuronal death via a number of possible mechanisms, including oxidative stress, excitotoxicity, energy depletion, inflammation and apoptosis. Despite this multifactorial etiology, genetics plays a key role in D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 0/ 20 17 7 :1 1: 17 P M