Shah Reena S, Lee Hyoung-Gon, Xiongwei Zhu, Perry George, Smith Mark A, Castellani Rudy J
Department of Neurology, University of Maryland, Baltimore, MD 21201, USA.
Biomed Pharmacother. 2008 Apr-May;62(4):199-207. doi: 10.1016/j.biopha.2008.02.005. Epub 2008 Mar 17.
The management of Alzheimer's disease (AD) has been a long-standing challenge and area of interest. Advances in knowledge of the pathogenesis of disease and an increase in disease burden have prompted investigation into innovative therapeutics over the last two decades. This article reviews the various treatments of AD including those targeted towards cholinergic deficiency, oxidative stress, the amyloid cascade, inflammation, and excitotoxicity. Second generation cholinesterase inhibitors remain the preferred therapy for early and intermediate AD while the glutamate antagonist, memantine, is also approved for advanced stages of disease. Antioxidants may delay disease progression, while data on other experimental therapies remain equivocal at best. Gene therapy directed at neurotropins is currently under investigation with some intriguing preliminary results; however, the number of patients examined is too few to be conclusive. Drugs directly targeting amyloid-beta, particularly the amyloid-beta vaccine, continue to be investigated and their forthcoming results are eagerly anticipated.
阿尔茨海默病(AD)的管理一直是一项长期挑战和研究热点。在过去二十年中,疾病发病机制知识的进步以及疾病负担的增加促使人们对创新疗法进行研究。本文综述了AD的各种治疗方法,包括针对胆碱能缺乏、氧化应激、淀粉样蛋白级联反应、炎症和兴奋性毒性的治疗方法。第二代胆碱酯酶抑制剂仍然是早期和中期AD的首选治疗方法,而谷氨酸拮抗剂美金刚也被批准用于疾病的晚期。抗氧化剂可能会延缓疾病进展,而其他实验性疗法的数据充其量也只是模棱两可。针对神经营养因子的基因治疗目前正在研究中,并有一些有趣的初步结果;然而,所检查的患者数量太少,无法得出结论。直接靶向β-淀粉样蛋白的药物,特别是β-淀粉样蛋白疫苗,仍在研究中,人们热切期待其即将公布的结果。