Allopregnanolone attenuates Aβ25-35-induced neurotoxicity in PC12 cells by reducing oxidative stress.

Massive accumulation of amyloid beta (Aβ) has been implicated as a pivotal event in the pathogenesis of Alzheimer's disease. The underlying mechanisms of Aβ-induced neurotoxicity include generation of reactive oxidative species (ROS), inflammation, and neurons loss. Allopregnano-lone (APα), a neurosteroid derive from neuroactive progesterone, has been demonstrated to have neuroprotective properties in vivo and vitro. In the present study, the effects of APα on oxidative damage in Aβ25-35-treated pheochromocytoma (PC12) cells were investigated. Pretreatment of APα significantly attenuated Aβ25-35-induced neuronal death. APα decreased the intracellular ROS generation and reduced lipid peroxidation induced by Aβ25-35. In addition, APα treatment enhanced antioxidant enzyme superoxide dismutase (SOD) activity. This study demonstrates that APα exerts a protective effect against Aβ25-35-induced neurotoxicity in PC12 cells. The protective role of APα likely results from inhibition of oxidative stress.