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

Area of Science:

• Pharmacology
• Neuroscience
• Drug Discovery

Background:

• The one-drug-one-target model faces challenges in complex diseases like Alzheimer's disease (AD).
• This has led to a "more funding, less drug" scenario in pharmaceutical research.
• Multitargeting strategies are needed to address the complexity of AD.

Purpose of the Study:

• To review synthetic and natural multipotent agents for Alzheimer's disease (AD).
• To evaluate agents targeting key AD pathologies such as acetylcholinesterase, monoamine oxidase, amyloid-beta, tau protein, metal ions, and reactive oxygen species.
• To assess the future potential of these multipotent agents in AD drug development.

Main Methods:

• Literature review of synthetic and natural compounds.
• Analysis of agents targeting multiple AD-related pathways.
• Evaluation of safety, absorbability, and pharmacokinetic profiles.

Main Results:

• Both synthetic and natural multipotent agents targeting key AD pathways have been identified.
• These agents demonstrate potential for hitting multiple targets implicated in AD.
• Natural compounds exhibit promising characteristics regarding safety, absorption, and pharmacokinetics compared to synthetic counterparts.

Conclusions:

• Multipotent agents offer a promising strategy for treating complex diseases like AD.
• Natural compounds are particularly promising due to favorable safety and pharmacokinetic profiles.
• Further development of natural multipotent agents could overcome limitations of the traditional drug discovery paradigm for AD.