a Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University , Xi'an , China.
b Institute of Holistic Integrated Medicine, Shaanxi University of Chinese Medicine , Shaanxi , Xianyang , China.
J Drug Target. 2019 Feb;27(2):164-173. doi: 10.1080/1061186X.2018.1474361. Epub 2018 Jun 20.
Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is considered as one of the most intractable medical problems with heavy social and economic costs. The current drugs for AD, including acetylcholinesterase inhibitors (AChEIs) and memantine, a NMDA receptor antagonist, only temporarily ameliorate cognitive decline, but are unable to stop or reverse the progression of dementia. This paper reviewed the recent advance in AD drug development. The drug discovery programs under clinical trials targeting cholinergic system, α7 nicotinic acetylcholine receptors (nAChRs), N-methyl-d-aspartate receptor (NMDAR), β-secretase, γ-secretase modulators, tau, inflammatory mediators and glucagon-like peptide-1 (GLP-1) were discussed. Though several drug discovery programs are ongoing, the high failure rate is an outstanding issue. Novel techniques and strategies are desperately needed to significantly accelerate this process.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，被认为是最棘手的医学问题之一，给社会和经济带来沉重负担。目前用于 AD 的药物，包括乙酰胆碱酯酶抑制剂（AChEIs）和 NMDA 受体拮抗剂美金刚，仅能暂时改善认知下降，但无法阻止或逆转痴呆的进展。本文综述了 AD 药物开发的最新进展。讨论了临床试验中针对胆碱能系统、α7 烟碱型乙酰胆碱受体（nAChRs）、N-甲基-D-天冬氨酸受体（NMDAR）、β-分泌酶、γ-分泌酶调节剂、tau、炎症介质和胰高血糖素样肽-1（GLP-1）的药物发现计划。尽管有几个药物发现计划正在进行中，但高失败率是一个突出的问题。迫切需要新的技术和策略来显著加快这一进程。
