17β-estradiol protects cerebellar granule cells against β-amyloid-induced toxicity via the apoptotic mitochondrial pathway.

Alzheimer's disease (AD) is a well-studied neurodegenerative disorder; nevertheless, significant therapeutic agents for the pharmacological treatment of this neuropathology are unavailable to date. The toxicity of amyloid beta-peptide (A beta) has been implicated as a critical cause in the development of AD, and A beta-amyloid-induced toxicity is typically associated with apoptosis. Here, we investigated the effect of 17 beta-estradiol (E2) on A beta-induced toxicity in cerebellar granule cells (CGCs). Our data showed a significant induction of apoptosis in neurons treated with A beta, and the addition of E2 reduced this effect. In addition, E2 reduced the A beta-induced up-regulation of Bax and down-regulation of Bcl-xL, and inhibited the subsequent mitochondrial release of cytochrome c and activation of caspase-3. Moreover, E2 inhibited A beta-induced c-Jun N-terminal protein kinase (JNK) activation. Taken together, these findings indicate that E2 protects against A beta-induced apoptosis in neuronal cells by preventing mitochondrial dysfunction and interfering with the JNK signalling cascade. (C) 2013 Elsevier Ireland Ltd. All rights reserved.