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

Abstract

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