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与能量代谢、胆碱能和单胺能神经传递有关的阿尔茨海默病新药。

Newly Developed Drugs for Alzheimer's Disease in Relation to Energy Metabolism, Cholinergic and Monoaminergic Neurotransmission.

机构信息

Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic.

Biomedical Research Centre, University Hospital Hradec Kralové, Sokolská 581, 500 05 Hradec Králové, Czech Republic; Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanského 62, 500 03 Hradec Králové, Czech Republic.

出版信息

Neuroscience. 2018 Feb 1;370:191-206. doi: 10.1016/j.neuroscience.2017.06.034. Epub 2017 Jul 1.

Abstract

Current options for Alzheimer's disease (AD) treatment are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or memantine, acting as an N-methyl-D-aspartate (NMDA). Therapeutic approaches vary and include novel cholinesterase inhibitors, modulators of NMDA receptors, monoamine oxidase (MAO) inhibitors, immunotherapeutics, modulators of mitochondrial permeability transition pores (mPTP), amyloid-beta binding alcohol dehydrogenase (ABAD) modulators, antioxidant agents, etc. The novel trends of AD therapy are focused on multiple targeted ligands, where mostly ChE inhibition is combined with additional biological properties, positively affecting neuronal energy metabolism as well as mitochondrial functions, and possessing antioxidant properties. The present review summarizes newly developed drugs targeting cholinesterase and MAO, as well as drugs affecting mitochondrial functions.

摘要

目前阿尔茨海默病(AD)的治疗选择基于乙酰胆碱酯酶抑制剂(多奈哌齐、利斯的明、加兰他敏)和/或 NMDA 的使用。治疗方法多种多样,包括新型乙酰胆碱酯酶抑制剂、NMDA 受体调节剂、单胺氧化酶(MAO)抑制剂、免疫疗法、线粒体通透性转换孔(mPTP)调节剂、β淀粉样蛋白结合醇脱氢酶(ABAD)调节剂、抗氧化剂等。AD 治疗的新趋势集中在多种靶向配体上,其中大多数胆碱酯酶抑制作用与其他生物特性相结合,积极影响神经元能量代谢和线粒体功能,并具有抗氧化特性。本综述总结了针对乙酰胆碱酯酶和 MAO 的新型药物以及影响线粒体功能的药物。

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