Estrogen protects neuronal cells from the cytotoxicity induced by acetylcholinesterase-amyloid complexes

The senile plaques present in Alzheimer's disease (AD) are composed of a core of amyloid beta-peptide (Abeta) plus several proteins including acetylcholinesterase (AChE). Recently we found that AChE forms complexes with the Abeta peptide in vitro and that these are more cytotoxic than Abeta fibrils alone. Considering that estrogen has been reported to act as a protective agent against Abeta-induced cytotoxicity, the effect of 17beta-estradiol was studied in rat pheochromocytoma (PC12) and mouse neuroblastoma (Neuro 2a) cells exposed to either Abeta alone or AChE-Abeta complexes. Estrogen showed a powerful protective effect in response to the challenge of AChE-Abeta complexes as well as with Abeta 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 Abeta fibrils and AChE-Abeta complexes, likely avoiding the free radical apoptotic pathway.