An insight into prodrug strategy for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. With 35 million people over 60 suffering from dementia, new treatments for AD are immediately needed. In order to streamline this process, it is critical to use insights and lessons learned from previous failures to future drug development efforts. Prodrugs have turned into a well-established delivery for increasing the physicochemical, pharmacokinetic or biological properties of pharmacologically potent candidates and overcoming hurdles to a drug’s usefulness in both drug research and development. In the present work, we focus on how prodrug strategy can leverage drug discovery to address drug development issues in AD. This review highlights the application of prodrug approach in treatment of AD by categorizing them into bio-oxidizable prodrugs, ester/amide prodrugs, pleiotropic prodrugs, linker-based prodrugs, Mannich base prodrugs, peptide-based and thiol-based prodrugs and gives an elaborate account of the research reported in the last two decades, i.e., from the year 2000 to 2021. Graphical abstract