Research progress in characterizing multiple-target mechanisms of novel anti-Alzheimer's dimers / 中国药理学通报

ABSTRACT

Alzheimer's disease ( AD ) is a complex disease caused by environmental and genetic factors. Therefore, one-drug-multiple-target compounds represent the most promising pharmacological approaches to preventing and treating this dis-ease. We have previously designed and synthesized bis( n)-Cog-nitin, novel anti-Alzheimer's dimers derived from tacrine. Bis ( n)-Cognitin have been proven to act on multiple important AD targets, including acetylcholinesterase, β-secretase, N-methyl-D-aspartic acid receptor and neuronal nitric oxide synthase, con-currently. Moreover, Bis(n)-Cognitin could inhibit β-amyloid-induced neurotoxicity, decrease glutamate-induced excitotoxici-ty, reduce oxidative stress, improve learning and memory, and protect against neuronal apoptosis in various in vitro and in vivo models, suggesting that bis ( n )-Cognitin are potential anti-AD drug candidates.