Qi et al
Abstract
Butyrylcholinesterase (BChE) has been considered as a potential therapeutic function for Alzheimer’s disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close relationship with Aβ deposit. Here, we identified S06-1011
(hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in Aβ1–42 peptide-induced
cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition
not only has a protective role against dementia but also exerts an effect on treatment and nursing care
