Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimer's Disease: A Review of Recent Clinical Studies
Effects of Cholinesterase Inhibitors on the Activities and Protein Levels of Cholinesterases in the Cerebrospinal Fluid of Patients with Alzheimer's Disease: A Review of Recent Clinical Studies
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DOI：
10.2174/156720510790274455
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发表时间：
2010-02-01
影响因子：
2.1
通讯作者：
Soininen, H.
中科院分区：
文献类型：
--
作者：
Darreh-Shori, T.;Soininen, H.
阿尔茨海默病(AD)是一种进行性神经退行性疾病，其特征是认知功能下降并伴有胆碱能功能缺陷。乙酰胆碱酯酶(AChE)和/或丁酰胆碱酯酶(BUCHE)的抑制剂，如多奈哌齐、加兰他明或利瓦斯汀，被广泛用作AD的对症治疗。这些药物在药理性质上表现出很大的差异。在这里，我们回顾了1998-2009年的临床数据，调查了不同的胆碱酯酶抑制剂治疗对AD患者脑脊液(CSF)中胆碱酯酶水平和活性的影响。这些研究表明，快速可逆胆碱酯酶抑制剂(如多奈哌齐、加兰他明、他克林)的治疗与AD患者脑脊液中AChE活性和蛋白水平的显著和显著上调有关。相反，假性不可逆胆碱酯酶抑制(如利凡斯明)与脑脊液AChE和BuChE活性显著降低有关，而脑脊液蛋白水平没有上调。此外，多奈哌齐与AChE-R亚型相对于突触AChE-S亚型的水平降低有关，而利瓦斯汀似乎增加了这一比例。这些发现表明，这些药物对脑脊液胆碱酯酶有不同的影响。这些药理差异的临床效果尚未完全确定。
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effects of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) is associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e. g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.