TL-2 attenuates beta -amyloid induced neuronal apoptosis through the AKT/GSK-3 beta / beta -cateni n pathway

• Published in: The international journal of neuropsychopharmacology 2014-09, Vol.17 (9), p.1511-1519
• Main Authors: Zhu, Xiaolei, Wang, Sulei, Yu, Linjie, Yang, Hui, Tan, Renxiang, Yin, Kailin, Jin, Jiali, Zhao, Hui, Guan, Dening, Xu, Yun
• Format: Article
• Language: English
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145714000315

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 sub(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 sub(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.