Activation of SIRT1 by curcumin blocks the neurotoxicity of amyloid-ß25-35 in rat cortical neurons.

ABSTRACT

As one of the most important hallmarks of Alzheimer's disease (AD), ß-amyloid (Aß) plays important roles in inducing reactive oxygen species (ROS) generation, mitochondrial dysfunction and apoptotic cell death in neurons. Curcumin extracted from the yellow pigments spice plant turmeric shows multiplied bioactivities such as antioxidant and anti-apoptosis properties in vitro and in vivo. In the present study, the neuroprotective effect of curcumin against Aß25-35-induced cell death in cultured cortical neurons was investigated. We found that pretreatment of curcumin prevented the cultured cortical neurons from Aß25-35-induced cell toxicity. In addition, curcumin improved mitochondrial membrane potential (ΔΨm), decreased ROS generation and inhibited apoptotic cell death in Aß25-35 treated neurons. Furthermore, we found that application of curcumin activated the expression of SIRT1 and subsequently decreased the expression of Bax in the presence of Aß25-35. The protective effect of curcumin was blocked by SIRT1 siRNA. Taken together, our results suggest that activation of SIRT1 is involved in the neuroprotective action of curcumin.