Awasthi Manika, Singh Swati, Pandey Veda P, Dwivedi Upendra N
Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, Department of Biochemistry, University of Lucknow, Lucknow 226007, India.
Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, Department of Biochemistry, University of Lucknow, Lucknow 226007, India.
J Neurol Sci. 2016 Feb 15;361:256-71. doi: 10.1016/j.jns.2016.01.008. Epub 2016 Jan 8.
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by amyloid beta (Aβ) deposition in brain with subsequent formation of neuritic plaques leading to dementia. A number of therapeutic strategies targeted against Aβ depositions have been rigorously explored which provided successful results corresponding to the existing symptomatic treatments. However, at the same time, several failures corresponding to the disease altering therapies and drugs have also been observed due to potential drawbacks in understanding of the pathogenesis of the disease, development of drug candidates and subsequent designing of clinical trials. Preclinical research, along with experimental and clinical studies, is continuously providing novel information which may reveal multi-target directed ligands and combination therapies for targeting Aβ. Thus, in view of the estimated increase in the number of AD patients globally, the present review attempts to summarize the available evidence dealing with various therapeutic approaches targeting Aβ, focusing specifically on pharmaceutical compounds under various stages of clinical trials. Furthermore, in view of a number of computational advances having significant impact in the field of computer aided drug design, we have also presented results of analysis of natural compounds as potential therapeutic molecules in preventing Aβ plaque formation using in silico approaches.
阿尔茨海默病（AD）是一种进行性且不可逆的神经退行性疾病，其特征是大脑中β淀粉样蛋白（Aβ）沉积，随后形成神经炎性斑块，导致痴呆。针对Aβ沉积的多种治疗策略已得到严格探索，这些策略取得了与现有对症治疗相对应的成功结果。然而，与此同时，由于在疾病发病机制理解、候选药物开发以及后续临床试验设计方面存在潜在缺陷，也观察到了一些与疾病改变疗法和药物相关的失败案例。临床前研究以及实验和临床研究不断提供新信息，这些信息可能揭示用于靶向Aβ的多靶点导向配体和联合疗法。因此，鉴于全球AD患者数量预计会增加，本综述试图总结有关针对Aβ的各种治疗方法的现有证据，特别关注处于临床试验不同阶段的药物化合物。此外，鉴于一些计算进展在计算机辅助药物设计领域产生了重大影响，我们还展示了使用计算机模拟方法分析天然化合物作为预防Aβ斑块形成的潜在治疗分子的结果。
