The Role of Butyrylcholinesterase in Alzheimer's Disease and Design Strategies of Its Inhibitors

In recent years, with the increase of life expectancy, the global population is aging. A variety of geriatric diseases have put a lot of pressure on the social security system and individual family life, and one of the most common geriatric diseases is Alzheimer's disease. Most of the experimental drugs currently in the clinical development for the treatment of AD are based on the cholinergic hypothesis. By inhibiting acetylcholinesterase (AChE), these medications raise the level of acetylcholine (ACh) in the brain of patients to improve cognitive function. However, this kind of drugs generally have some problems, such as poor efficacy in patients with the mid- to late-stage AD, and significant side effects. In the brains of the patients with the mid- and late-stage AD, AChE levels declines abnormally, whereas the level of butyrylcholinesterase (BChE), which also hydrolyzes ACh, rises compensatingly. Therefore, inhibition of BChE becomes a better choice at this time. Additionally, BChE has a good safety profile as a target, and selective inhibition of BChE doesn't cause the peripheral side effects similar to those of AChE inhibitors. This article has reviewed the advances in research on the role of BChE in Alzheimer's disease and the design strategies of BChE inhibitors.