dalesconol-b and Memory-Disorders

β-amyloid (Aβ)-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 Aβ-induced apoptosis in vitro and in vivo and to explore the underlying mechanisms. Aβ(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 Aβ(1-42)-induced neuronal apoptosis in vitro and in vivo. In addition, TL-2 could activate the AKT/GSK-3β pathway, and inhibition of AKT and activation of GSK-3β 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-3β pathway to promote neuronal survival. These results suggest that TL-2 might be a potential drug for AD treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; beta Catenin; Caspase 3; Caspase 9; Cells, Cultured; Cerebral Cortex; Chromones; Disease Models, Animal; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Maze Learning; Memory Disorders; Mice; Morpholines; Neurons; Neuroprotective Agents; Oncogene Protein v-akt; Peptide Fragments; Polycyclic Aromatic Hydrocarbons; Signal Transduction