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

The accumulation of amyloid-beta (A beta), considered as the major cause of Alzheimer's disease (AD) pathogenesis, relays on the rate of its biosynthesis and degradation. A beta degradation is a common overture to late-onset AD and targeting the impairment of A beta degradation has gained attention in the recent years. In this study, we demonstrated a rhamnoside derivative PL402 suppressed A beta level in cell models without changing the expression or activity of A beta 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 A beta via MMP3/9-mediated A beta degradation. Notably, administration of PL402 significantly attenuated A beta pathology and cognitive defects in APP/PS1 transgenic mice with the consistent promotion of ADEs expression. Thus, our study suggests that targeting A beta degradation could be an effective strategy against AD and the rhamnoside derivatives may have therapeutic effects.