Liu Haibin, Wang Lirong, Su Weiwei, Xie Xiang-Qun
Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, School of Pharmacy, NIDA Center of Excellence for Computational Drug Abuse Research, Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Pharm Pat Anal. 2014 Jul;3(4):429-47. doi: 10.4155/ppa.14.22.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, involving a large number of genes, proteins and their complex interactions. Currently, no effective therapeutic agents are available to either stop or reverse the progression of this disease, likely due to its polygenic nature. The complicated pathophysiology of AD remains unresolved. Although it has been hypothesized that the amyloid β cascade and the hyper-phosphorylated tau protein may be primarily involved, other mechanisms, such as oxidative stress, deficiency of central cholinergic neurotransmitter, mitochondrial dysfunction and inflammation have also been implicated. The main focus of this review is to document current therapeutic agents in clinical trials and patented candidate compounds under development based on their main mechanisms of action. It also discusses the relationship between the recent understanding of key targets and the development of potential therapeutic agents for the treatment of AD.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,涉及大量基因、蛋白质及其复杂的相互作用。目前,由于其多基因性质,尚无有效的治疗药物能够阻止或逆转该疾病的进展。AD复杂的病理生理学仍未得到解决。尽管有假说认为淀粉样β蛋白级联反应和过度磷酸化的tau蛋白可能起主要作用,但其他机制,如氧化应激、中枢胆碱能神经递质缺乏、线粒体功能障碍和炎症也被认为与之相关。本综述的主要重点是根据其主要作用机制记录目前正在进行临床试验的治疗药物以及正在研发的专利候选化合物。它还讨论了对关键靶点的最新认识与治疗AD潜在治疗药物开发之间的关系。