One-compound-multiple-targets strategy to combat Alzheimer's disease.

The present one-drug-one-target paradigm in drug discovery has been considered partially responsible for the more-funding-less-drug predicament in modern pharmaceutical industry. To hit the multiple targets implicated in complex diseases, two strategies, based on multicomponent or single-ingredient, are conceivable. Although the latter is more difficult to be fulfilled than the former, the recent progress made in the fight against Alzheimer's disease (AD) has brought us the first light of success of the latter strategy. In this review, both synthetic and natural multipotent agents are described, which hit two or more targets implicated in AD, e.g., acetylcholinesterase, monoamine oxidase, amyloid-beta, tau protein, metal ions and reactive oxygen species. Nevertheless, due to the potential risks in safety, absorbability and pharmacokinetics of synthetic multipotent agents, natural counterparts seem more promising in the future development.