Abstract

The senile plaques present in Alzheimer's disease (AD) are composed of a core of amyloid beta-peptide (A beta) plus several proteins including acetylcholinesterase (AChE). Recently we found that AChE forms complexes with the A beta peptide in vitro and that these are more cytotoxic than A beta fibrils alone, Considering that estrogen has been reported to act as a protective agent against A beta-induced cytotoxicity, the effect of 17 beta-estradiol was studied in rat pheochromocytoma (PC12) and mouse neuroblastoma (Neuro 2a) cells exposed to either A beta alone or AChE-A beta completes. Estrogen showed a powerful protective effect in response to the challenge of AChE-A beta complexes as well as with A beta fibrils. This was also the case for other cytotoxic agents such as glutamate and H2O2. Our results suggest a common mechanism for cellular protection by estrogen against the toxicity of both A beta fibrils and AChE-A beta complexes, likely avoiding the free radical apoptotic pathway. (C) 1998 Federation of European Biochemical Societies.