TL-2 attenuates β-amyloid induced neuronal apoptosis through the AKT/GSK-3β/β-catenin pathway.

β -amyloid (A β )-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 β -induced apoptosis in vitro and in vivo and to explore the underlying mechanisms. A β 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 β 1–42-induced neuronal apoptosis in vitro and in vivo . In addition, TL-2 could activate the AKT/GSK-3 β pathway, and inhibition of AKT and activation of GSK-3 β partially eliminated the neuroprotective effects of TL-2. Furthermore, TL-2 induced the nuclear translocation of β -catenin and enhanced its transcriptional activity through the AKT/GSK-3 β pathway to promote neuronal survival. These results suggest that TL-2 might be a potential drug for AD treatment.