摘要
背景:乙酰胆碱酯酶(AChE)通过在中枢和周围神经系统的许多胆碱能途径中迅速水解神经递质乙酰胆碱来参与脉冲传递的终止。酶失活导致乙酰胆碱积聚,烟碱和毒蕈碱受体过度刺激,并破坏神经传递。因此,与酶作为其主要靶标相互作用的乙酰胆碱酯酶抑制剂被用作不同神经变性疾病(如阿尔茨海默病和帕金森氏症)以及毒素的相关药物。同时,越来越多的证据表明,在非神经元背景下,AChE参与细胞增殖,分化,细胞凋亡和细胞 - 细胞相互作用的调控。在不同类型的肿瘤中发现AChE的不规则表达,表明AChE参与肿瘤发展的调节。考虑到这一点,有可能使用一些AChE抑制剂作为抗癌剂。 目的:这一贡献将讨论广泛的可能应用不同的AChE抑制剂作为药物,从众所周知的抗阿尔茨海默氏病药物在未来用于癌症治疗。将重点介绍各种已知的AChE抑制剂类,其作为药物的应用可能引起争议,以及新调查的天然产物,其也可以调节AChE活性。结论:患者治疗神经退行性疾病易发生某些类型癌症风险升高并不清楚,反之亦然。对于基于AChE作为靶分子的所有疗法,在理性药物设计过程中,必须牢记这一点。
关键词: 乙酰胆碱酯酶,阿尔茨海默病,帕金森病,癌症治疗,药物设计,细胞凋亡。
Current Medicinal Chemistry
Title:Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti-Cancer Drugs
Volume: 24 Issue: 30
关键词: 乙酰胆碱酯酶,阿尔茨海默病,帕金森病,癌症治疗,药物设计,细胞凋亡。
摘要: Background: Acetylcholinesterase (AChE) is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs for different neurodegenerative diseases (such as Alzheimer's and Parkinson's) as well as toxins. At the same time, there are increasing evidence that in non-neuronal context, AChE is involved in the regulation of cell proliferation, differentiation, apoptosis and cell-cell interaction. An irregular expression of AChE has been found in different types of tumors, suggesting the involvement of AChE in the regulation of tumor development. Having all this in mind, there is a possibility that some AChE inhibitors could be used as anti-cancer agents.
Objective: This contribution will discuss a broad range of possible application of different AChE inhibitors as drugs, from well-known anti-Alzheimer's disease drugs to their use in cancer treatment in future. Emphasis will be put on various known AChE inhibitors classes, whose application as drugs could be controversy, as well as on newly investigated natural products, which can also modulate AChE activity.
Conclusion: It is not clear a patient treated for neurodegenerative condition prone to increased risk for some types of cancer and vice versa. This is necessary to keep in mind during rational drug design process for all therapies, which are based on AChE as a target molecule.
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Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti-Cancer Drugs, Current Medicinal Chemistry 2017; 24 (30) . https://dx.doi.org/10.2174/0929867324666170705123509
DOI https://dx.doi.org/10.2174/0929867324666170705123509 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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