Identification of "sarsasapogenin-aglyconed" timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing.

ABSTRACT: The inhibition of amyloid β (Aβ) peptide production is a key approach in the development of therapeutics for the treatment of Alzheimer's disease (AD). We have identified that timosaponins consisting of sarsasapogenin (SSG) as the aglycone can effectively lower the production of Aβ peptides and stimulate neurite outgrowth in neuronal cell cultures. Structure-activity relationship studies revealed that the cis-fused AB ring, 3β-configuration, spiroketal F-ring and 25S-configuration of SSG are the essential structural features responsible for the Aβ-lowering effects and neurite-stimulatory activity. New synthetic derivatives that retain the SSG scaffold also exhibited an Aβ lowering effect. Treatment of cells with timosaponins led to modulation of amyloid precursor protein (APP

SUBMITTER: Sy LK 

PROVIDER: S-EPMC6005341 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature