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阿尔茨海默病的药物治疗:当前方法与未来策略

Pharmacological treatment for Alzheimer's disease: current approaches and future strategies.

作者信息

Fan Ling-Yun, Chiu Ming-Jang

机构信息

Department of Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Acta Neurol Taiwan. 2010 Dec;19(4):228-45.

Abstract

More than a decade after the first approval of the use of acetylcholine esterase inhibitor on patients with Alzheimer's disease, we still not have a single treatment or combination therapy that can effectively stop or reverse the relentless progression of such neurodegenerative disease. Recently therapeutics targeting amyloid hypothesis have undergone scrutiny by many clinical trials. These include gamma secretase inhibitor for reducing beta amyloid formation, agents for preventing aggregation of amyloid oligomers, and immunotherapy for enhancing clearance of amyloid and plaque. Therapies targeting hyperphosphorylated tau is another promising mechanism to be tackled with. Other agents enforcing mitochondria functions, enhancing serotonin receptors, modulating advanced glycation end products, and neurotrophic factors, as well as other therapies are also emerging. We review current treatments and therapeutic strategies already undergone different stage of clinical trails in this report. We propose that therapeutics of various combination composed of symptomatic treatments and disease modifying therapies will become standard regimens of AD treatment with much better efficacy than current approaches.

摘要

在乙酰胆碱酯酶抑制剂首次被批准用于治疗阿尔茨海默病患者十多年后,我们仍然没有一种单一的治疗方法或联合疗法能够有效阻止或逆转这种神经退行性疾病无情的进展。最近,针对淀粉样蛋白假说的疗法已经在许多临床试验中接受了审查。这些疗法包括用于减少β淀粉样蛋白形成的γ分泌酶抑制剂、用于防止淀粉样寡聚体聚集的药物以及用于增强淀粉样蛋白和斑块清除的免疫疗法。针对过度磷酸化tau蛋白的疗法是另一个有待解决的有前景的机制。其他增强线粒体功能、增强5-羟色胺受体、调节晚期糖基化终产物和神经营养因子的药物以及其他疗法也正在出现。在本报告中,我们回顾了目前已经经历了不同临床试验阶段的治疗方法和治疗策略。我们提出,由对症治疗和疾病修饰疗法组成的各种联合疗法将成为阿尔茨海默病治疗的标准方案,其疗效将比目前的方法好得多。

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