RESUMO
Although oligomeric ß-amyloid (Aß) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aß induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aß-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aß. Here, we found that treatment with oligomeric Aß increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aß-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aß-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD.