Progress in Alzheimer's disease drug discovery: an update.
Progress in Alzheimer's disease drug discovery: an update.
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阿尔茨海默病药物发现进展：更新。
DOI：
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发表时间：
2009
影响因子：
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通讯作者：
Michael Williams
中科院分区：
文献类型：
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作者：
Michael Williams
虽然阿尔茨海默氏病（AD）是一个重大的医疗挑战，目前全球有2500万至3400万人受到影响，预计到2050年将有三倍的患者，但目前批准用于AD姑息治疗的药物，胆碱酯酶抑制剂和NMDA拮抗剂美金刚胺，已经证明了可疑的疗效，突出了对新疗法的迫切需求。针对AD患者大脑中淀粉样蛋白斑块清除的努力令人失望，无论是斑块清除疫苗还是γ-分泌酶调节剂tarenflurbil都没有表现出临床益处，因此质疑过去十年驱动AD研究的淀粉样蛋白级联假说的有效性。在开发新的AD药物的机制方法（淀粉样蛋白和tau假设）方面缺乏进展，表明AD因果关系的一些基本假设和寻找有效药物可能需要进行重大的重新评估和重新定向。
While Alzheimer's disease (AD) represents a major healthcare challenge, with 25 to 34 million individuals currently affected worldwide and triple this number of patients projected by 2050, the drugs currently approved for the palliative treatment of AD, the cholinesterase inhibitors and the NMDA antagonist memantine, have demonstrated questionable efficacy, highlighting an urgent need for new therapies. Efforts in targeting the removal of amyloid plaques from the brain of patients with AD have been disappointing, with neither plaque-removing vaccines nor the gamma-secretase modulator, tarenflurbil demonstrating clinical benefit, thus questioning the validity of the amyloid cascade hypothesis that has driven AD research for the past decade. The lack of progress in mechanistic approaches (the amyloid and tau hypotheses) to developing new AD drugs indicates that some of the basic assumptions of AD causality and the search for effective drugs are probably in need of major reassessment and redirection.