Huperzine A and tacrine attenuate β-amyloid peptide-induced oxidative injury

Increased oxidative stress resulting from free radical damage to cellular function is associated with a number of neurodegenerative diseases, in particular with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (A beta), the major pathological hallmark for AD, has been suggested as the central disease-causing and disease-promoting event for the disease, and the pathological role of A beta was partially mediated by oxidative stress. Here we compared the effects of huperzine A (HupA) and tacrine, two acetylcholinesterase (AChE) inhibitors available for AD, on A beta-induced cell lesion, level of lipid peroxidation, and antioxidant enzyme activities in rat PC12 and primary cultured cortical neurons. Following exposure of both cells to different concentrations of an active fragment of A beta, a marked reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MDA) and superoxide dismutase (SOD), were observed. Pretreatment of the cells with HupA or tacrine (0.1-10 mu M) prior to A beta exposure significantly elevated the cell survival and GSH-Px and CAT activities and decreased the level of MDA. Both drugs have similar protection against A beta insult. Our results indicate that HupA and tacrine exert neuroprotective effects against A beta toxicity, which might be of importance and might contribute to their clinical efficacy for the treatment of AD. (C) 2000 Wiley-Liss, Inc.