Inhibition of β-site amyloid precursor protein cleaving enzyme 1 and cholinesterases by pterosins via a specific structure−activity relationship with a strong BBB permeability

Abstract

Alzheimer’s disease: Promising therapeutic compounds found in plants Compounds extracted from bracken fern block the activity of three enzymes associated with Alzheimer’s disease (AD). Because AD is a complex and multifactorial disease, a multitarget-directed approach is an attractive strategy for the development of disease-modifying therapeutics. A study led by Gil Hong Park, Korea University, Seoul, and Nam Sook Kang, Chungnam National University, Daejon, revealed that pterosin derivatives could reduce the activity of β-site amyloid precursor protein cleaving enzyme 1, acetylcholinesterase and butyrylcholinesterase in a concentration-dependent manner. Furthermore, the fern-extracted compounds did not cause cellular toxicity and were able to cross the blood–brain barrier, which is impermeable to most drugs, to reach the brain. Future studies will determine whether they can be developed into drugs to simultaneously engage various AD targets in animal models of the disease.