A novel rhamnoside derivative PL402 up-regulates matrix metalloproteinase 3/9 to promote Aβ degradation and alleviates Alzheimer's-like pathology.

ABSTRACT: The accumulation of amyloid-β (Aβ), considered as the major cause of Alzheimer's disease (AD) pathogenesis, relays on the rate of its biosynthesis and degradation. Aβ degradation is a common overture to late-onset AD and targeting the impairment of Aβ degradation has gained attention in the recent years. In this study, we demonstrated a rhamnoside derivative PL402 suppressed Aβ level in cell models without changing the expression or activity of Aβ generation-related secretases. However, the levels of matrix metalloproteinase (MMP) 3 and 9, belonging to amyloid-degrading enzymes (ADEs), were up-regulated by PL402. The inhibition or the knockdown of these two enzymes abolished the effect of PL402, indicating that PL402 may reduce Aβ via MMP3/9-mediated Aβ degradation. Notably, administration

SUBMITTER: Hu T 

PROVIDER: S-EPMC6977668 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature