Nordberg Agneta, Ballard Clive, Bullock Roger, Darreh-Shori Taher, Somogyi Monique
Alzheimer Neurobiology Center, Karolinska Institute, Stockholm, Sweden (Drs Nordberg and Darreh-Shori); Wolfson Centre for Age-Related Diseases, King's College, London, United Kingdom (Dr Ballard); Kingshill Research Centre, Victoria Hospital, Swindon, United Kingdom (Dr Bullock); and Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (Dr Somogyi).
Prim Care Companion CNS Disord. 2013;15(2). doi: 10.4088/PCC.12r01412. Epub 2013 Mar 7.
To examine the role of butyrylcholinesterase (BuChE) in cholinergic signaling and neurologic conditions, such as Alzheimer's disease (AD). The rationale for inhibiting cholinesterases in the management of AD, including clinical evidence supporting use of the dual acetylcholinesterase (AChE) and BuChE inhibitor rivastigmine, is discussed.
PubMed searches were performed using butyrylcholinesterase as a keyword. English-language articles referenced in PubMed as of September 2011 were included. Study Selection and Data Synthesis: English-language articles related to BuChE considered to be of clinical relevance to physicians were included. English-language articles specifically related to AChE were not included, as the role of AChE in cholinergic signaling and the underlying pathology of AD is well documented. Reference lists of included publications were used to supplement the search.
AChE and BuChE play a role in cholinergic signaling; BuChE can hydrolyze acetylcholine and compensate for AChE when levels are depleted. In the AD brain, AChE levels decrease, while BuChE levels are reportedly increased or unchanged, with changes becoming more pronounced during the disease course. Furthermore, BuChE genotype may influence AD risk and rate of disease progression. Strategies that increase acetylcholine levels (eg, cholinesterase inhibitors) demonstrate symptomatic efficacy in AD. Rivastigmine has proven cognitive efficacy in clinical trials, and data suggest that its action is mediated, in part, by inhibition of BuChE. Retrospective analyses of clinical trials provide evidence that BuChE genotype may also influence treatment response.
AChE-selective inhibitors and a dual AChE and BuChE inhibitor demonstrate symptomatic efficacy in AD. Mounting preclinical and clinical evidence for a role of BuChE in maintaining normal cholinergic function and the pathology of AD provides a rationale for further studies investigating use of rivastigmine in AD and the influence of BuChE genotype on observed efficacy.
研究丁酰胆碱酯酶（BuChE）在胆碱能信号传导及神经系统疾病（如阿尔茨海默病（AD））中的作用。讨论了在AD治疗中抑制胆碱酯酶的理论依据，包括支持使用双乙酰胆碱酯酶（AChE）和BuChE抑制剂卡巴拉汀的临床证据。
以丁酰胆碱酯酶为关键词在PubMed上进行检索。纳入截至2011年9月PubMed中引用的英文文章。研究选择与数据综合：纳入被认为对医生具有临床相关性的与BuChE相关的英文文章。不包括与AChE具体相关的英文文章，因为AChE在胆碱能信号传导及AD潜在病理方面的作用已有充分记录。利用纳入出版物的参考文献列表补充检索。
AChE和BuChE在胆碱能信号传导中发挥作用；当AChE水平降低时，BuChE可水解乙酰胆碱并起到补偿作用。在AD患者大脑中，AChE水平下降，而据报道BuChE水平升高或不变，且在疾病过程中变化更为明显。此外，BuChE基因型可能影响AD风险和疾病进展速度。提高乙酰胆碱水平的策略（如胆碱酯酶抑制剂）在AD中显示出症状改善疗效。卡巴拉汀在临床试验中已证明具有认知疗效，数据表明其作用部分是通过抑制BuChE介导的。临床试验的回顾性分析提供证据表明BuChE基因型也可能影响治疗反应。
AChE选择性抑制剂以及双AChE和BuChE抑制剂在AD中显示出症状改善疗效。越来越多的临床前和临床证据表明BuChE在维持正常胆碱能功能及AD病理过程中发挥作用，这为进一步研究卡巴拉汀在AD中的应用以及BuChE基因型对观察到的疗效的影响提供了理论依据。
