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

Increased oxidative stress resulting from free radical damage to cellular f unction is associated with a number of neurodegenerative diseases, in parti cular with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (A beta), the major pathological hallmark for AD, has been suggested as th e 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 acetyl cholinesterase (AChE) inhibitors available for AD, on A beta-induced cell l esion, level of lipid peroxidation, and antioxidant enzyme activities in ra t PC12 and primary cultured cortical neurons. Following exposure of both ce lls to different concentrations of an active fragment of A beta, a marked r eduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MD A) 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 again st A beta toxicity, which might be of importance and might contribute to th eir clinical efficacy for the treatment of AD. (C) 2000 Wiley-Liss, Inc.