Cholinergic function and Alzheimer's disease
Cholinergic function and Alzheimer's disease
复制标题
DOI：
10.1002/gps.935
复制
发表时间：
2003-09-01
影响因子：
4
通讯作者：
Giacobini, E
中科院分区：
文献类型：
--
作者：
Giacobini, E
胆碱能功能缺陷导致阿尔茨海默病(AD)的病理，影响认知、行为和日常生活活动。针对这些缺陷的药物干预是基于对乙酰胆碱酯酶(AChE)的抑制。这些药物是否已经达到了治疗的‘天花板’是一个悬而未决的问题，胆碱能干预可能与其他治疗机制有效地结合在一起。与这类问题有关的数据仍在收集中。重度AD患者AChE和胆碱乙酰转移酶水平较正常下降90%，而丁酰胆碱酯酶(BUCHE)升高。在这种情况下，BuChE可能是更合适的治疗靶点。AChE和BuChE都与β-淀粉样蛋白一起聚集在老年斑中，目前正在进行研究，以确定是否可以开发出既抑制AChE又作用于β-淀粉样蛋白的药物。尼古丁结合位点的缺失给新的尼古丁药物带来了希望。胆碱能疗法可能会引起不受欢迎的副作用，寻找“理想的”抑制剂的工作仍在继续。联合用药最终可能被证明是治疗阿尔茨海默病患者最有效的方法。版权所有(C)2003 John Wiley Sons，Ltd.
Deficits in cholinergic function contribute to the pathology of Alzheimer's disease (AD), affecting cognition, behaviour and activities of daily living. Pharmacological intervention directed towards these deficits is based on acetylcholinesterase (AChE) inhibition. Whether such drugs have reached their therapeutic 'ceiling' is an open question and it is possible that cholinergic intervention may be usefully combined with other therapeutic mechanisms. Data relating to such issues are still being collected. In severe AD, levels of AChE and choline acetyltransferase are decreased by as much as 90% compared with normal, whilst butyrylcholinesterase (BuChE) increases. In such instances, it is possible that BuChE may be a more appropriate therapeutic target. Both AChE and BuChE are aggregated in senile plaques along with beta-amyloid, and investigations are being undertaken to determine whether drugs can be developed that inhibit AChE whilst also acting on beta-amyloid. Deficits in nicotinic binding sites have led to hopes for new nicotinic drugs. Cholinergic therapies can potentially cause unwanted side effects and the search for the 'ideal' inhibitor continues. Combinations of drugs may ultimately prove to be the most productive means of treating patients with AD. Copyright (C) 2003 John Wiley Sons, Ltd.