Alzheimer's disease (AD), characterized by progressive memory loss, decline in language skills and other cognitive impairments, has been a major threat to ageing population.
A recent paper in the October issue of FEBS Letters, reviews the different strategies in drug discovery. Hong-Yu Zhang, the author of the study, muses that the success of the present one-drug-one-target strategy in drug discovery is limited, which has stimulated the search for more efficient combined weapons to combat AD. Drug discovery paradigm is now shifting from one-drug-one-target strategy to one-drug-multiple-targets strategy. The diverse targets can be hit not only by multiple components but also by one compound or even by a single pharmacophore.
To hit the multiple targets implicated in the complex diseases, two strategies are conceivable. One is called multi-component therapeutic strategy, which incorporates two or more active ingredients in one drug. In fact, this strategy has been successfully used in traditional medicine for thousands of years and in current drug cocktails as well to suppress the spreading of HIV.
The other strategy attempts to employ one compound to hit the multiple targets, which can be termed as one-compound-multiple-targets strategy. Although the latter strategy seems more convenient than the former, it is more difficult to be fulfilled. Nevertheless, the accumulating experience gained in the battle against AD displays the feasibility 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-â, ô 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.