Tl-2 Attenuates Beta-Amyloid Induced Neuronal Apoptosis Through The Akt/Gsk-3 Beta/Beta-Catenin Pathway

beta-amyloid (A beta)-mediated neuronal apoptosis contributes to the progression of Alzheimer's disease (AD), although the exact mechanism remains unclear. This study aimed to investigate whether Dalesconol B (TL-2), a potent immunosuppressive agent with an unusual carbon skeleton, could inhibit A beta-induced apoptosis in vitro and in vivo and to explore the underlying mechanisms. A beta(1-42) was injected to bilateral hippocampus of mice to make the AD models in vivo. TL-2 was able to cross the blood-brain barrier and attenuate memory deficits in the AD mice. TL-2 also inhibited A beta(1-42)-induced neuronal apoptosis in vitro and in vivo. In addition, TL-2 could activate the AKT/GSK-3 beta pathway, and inhibition of AKT and activation of GSK-3 beta partially eliminated the neuroprotective effects of TL-2. Furthermore, TL-2 induced the nuclear translocation of beta-catenin and enhanced its transcriptional activity through the AKT/GSK-3 beta pathway to promote neuronal survival. These results suggest that TL-2 might be a potential drug for AD treatment.