Macdonald Ian R, Rockwood Kenneth, Martin Earl, Darvesh Sultan
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada.
J Alzheimers Dis. 2014;42(2):379-84. doi: 10.3233/JAD-140219.
Cholinesterase inhibitors are the standard of care for Alzheimer's disease (AD). Acetylcholinesterase (AChE) catalyzes the hydrolysis of the cholinergic neurotransmitter acetylcholine. However, the related enzyme butyrylcholinesterase (BuChE) also breaks down acetylcholine and is likewise targeted by the same clinical cholinesterase inhibitors. The lack of clinical efficacy for the highly specific and potent AChE inhibitor, (-) huperzine A, is intriguing, given the known cholinergic deficit in AD. Based on the proven efficacy of inhibitors affecting both cholinesterases and the apparent failure of specific AChE inhibition, focused BuChE inhibition seems important for more effective treatment of AD. Therefore, BuChE-selective inhibitors provide promise for improved benefit.
胆碱酯酶抑制剂是治疗阿尔茨海默病（AD）的标准药物。乙酰胆碱酯酶（AChE）催化胆碱能神经递质乙酰胆碱的水解。然而，相关酶丁酰胆碱酯酶（BuChE）也能分解乙酰胆碱，并且同样是临床胆碱酯酶抑制剂的作用靶点。鉴于AD中已知的胆碱能缺陷，高度特异性和强效的AChE抑制剂（-）石杉碱甲缺乏临床疗效这一点令人费解。基于影响两种胆碱酯酶的抑制剂已证实的疗效以及特异性AChE抑制的明显失败，针对性地抑制BuChE对于更有效地治疗AD似乎很重要。因此，BuChE选择性抑制剂有望带来更好的疗效。
