Ashraf Ghulam Md, Tabrez Shams, Jabir Nasimudeen R, Firoz C K, Ahmad Saheem, Hassan Iftekhar, Alexiou Athanasios, Kamal Mohammad Amjad
King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia.
Curr Drug Metab. 2015;16(8):719-27. doi: 10.2174/138920021608151107125757.
Despite extensive research for over two decades, the medical science is yet to assign the exact aetiology and mode of progression of Alzheimer's disease (AD). The modern era of AD drug development began with the proposal of the cholinergic hypothesis of memory impairment. Since then, despite the proposal and phase trials of many therapeutic options, only few drugs have shown some efficacy and safety. The reasons behind this have been many including the ineffectiveness of tested drugs and inadequacy of clinical development methods. In this manuscript, we present an account of modern structural, functional and molecular imaging developed for AD therapy. A comprehensive review of all the current and future treatment options for AD, ranging from cholinergic drugs, NMDA receptor antagonist, immunotherapy, drugs reducing Aβ production, and drugs targeting tau protein and mitochondrial dysfunction has also been provided. However, the failure of all the proposed treatment options to provide a complete cure of AD has been pushing for the need of new therapies. The recent advent of nano-drugs has been proposed to provide crucial breakthroughs in AD therapy. Hence, a detailed outline of the usage and applications of nano-drugs in AD therapy, and outstanding developments in nanodrug metabolism and disposition has been discussed.
尽管经过二十多年的广泛研究,医学仍未确定阿尔茨海默病(AD)的确切病因和进展模式。AD药物研发的现代时代始于记忆障碍胆碱能假说的提出。从那时起,尽管有许多治疗方案被提出并进行了临床试验阶段,但只有少数药物显示出一定的疗效和安全性。其背后的原因有很多,包括受试药物无效以及临床开发方法不足等。在本手稿中,我们介绍了为AD治疗而开发的现代结构、功能和分子成像技术。还对AD目前和未来所有的治疗选择进行了全面综述,范围涵盖胆碱能药物、NMDA受体拮抗剂、免疫疗法、减少Aβ生成的药物以及针对tau蛋白和线粒体功能障碍的药物。然而,所有提出的治疗方案都未能完全治愈AD,这促使人们需要新的疗法。最近纳米药物的出现被认为有望在AD治疗中取得关键突破。因此,本文讨论了纳米药物在AD治疗中的使用和应用细节,以及纳米药物代谢和处置方面的显著进展。