Ontology highlight
ABSTRACT: Background
Alzheimer's disease (AD) involves impairment of Aβ clearance. Neprilysin (NEP) is the most efficient Aβ peptidase. Enhancement of the activity or expression of NEP may provide a prominent therapeutic strategy against AD.Aims
Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized and evaluated for their NEP upregulating potential using sensitive fluorescence-based Aβ digestion and inhibition assays.Results
Compound 4 was the most active one, resulting in a 50% increase in Aβ cleavage activity. Cyclohexanone-bearing derivatives exhibited higher activity enhancement compared to their acetone counterparts. Inhibition experiments with the NEP-specific inhibitor thiorphan resulted in dramatic cleavage reduction. Conclusion: The increased Aβ cleavage activity and the ease of synthesis of 4 renders it an extremely attractive lead compound.
SUBMITTER: Matiadis D
PROVIDER: S-EPMC8394082 | biostudies-literature |
REPOSITORIES: biostudies-literature