Lao_2018_J.Drug.Target__1

Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is considered 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, alpha7 nicotinic acetylcholine receptors (nAChRs), N-methyl-D-aspartate receptor (NMDAR), beta-secretase, gamma-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 to significantly accelerate this process.