A beta regulation-based multitarget strategy for drug discovery against Alzheimer's disease

作者：Guo Xiaodan; Jiang Wei; Li Chenjing; Zhu Zhiyuan^*; Shen Xu

来源：Reviews in the Neurosciences, 2015, 26(1): 13-30.

DOI：10.1515/revneuro-2014-0064

• acetyl cholinesterase
• Alzheimer's disease
• autophagy
• beta-amyloid
• ER stress
• lifespan
• multitarget
• oxidative stress
• secretase
• tau protein

Alzheimer's disease (AD) is a progressively neurodegenerative disease that eventually leads to the irreversible loss of neurons and intellectual abilities, including cognition and memory. AD has become the most common cause of dementia in aged people, and the ill-defined pathogenesis of AD is seriously impeding the current drug discovery against this disease. To date, there is still a lack of etiologically therapeutic drugs for AD, although some symptomatic treatments have been successfully developed. The beta-amyloid (A beta)-induced neurodegeneration is determined as the main pathogenesis of AD, and by targeting the regulation of A beta in production inhibition or clearance promotion, many active agents have been designed potentially for AD treatment, but no drug has yet been approved in clinical use. Actually, AD has a complex pathogenic mechanism that involves multiple aberrant signaling genes and pathways, and the idea of 'single target' for anti-AD drug research is thus full of challenges. Recently, with a deep understanding of AD pathogeneses and the development of advanced pharmacological techniques, 'multiple target'-based strategy has been widely applied for the drug discovery against this disease, and many promising results have been achieved. Here, we review the recent multitarget strategies for the drug discovery in the treatment of AD by focusing on the involvement of A beta regulation.

• 出版日期2015-2
• 单位中国科学院; 中国科学院上海药物研究所