丁酰胆碱酯酶
乙酰胆碱酯酶
胆碱能的
医学
胆碱酯酶
乙酰胆碱
竞争对手
阿切
药理学
阿尔茨海默病
疾病
神经科学
内科学
多奈哌齐
酶
痴呆
生物化学
生物
作者
Nigel H. Greig,Tadanobu Utsuki,Qian-sheng Yu,Xiaoxiang Zhu,Harold W. Holloway,TracyAnn Perry,Bong Lee,Donald K. Ingram,Debomoy K. Lahiri
标识
DOI:10.1185/0300799039117057
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.
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