Going beyond ATP binding site as a novel inhibitor design strategy for tau protein kinases in the treatment of alzheimer's disease: A review

Alzheimer's disease (AD) is among the top mortality causing diseases worldwide. The presence of extracellular β-amyloidosis, as well as intraneuronal neurofibrillary aggregates of the abnormally hyperphosphorylated tau protein are two major characteristics of AD. Targeting protein kinases that are involved in the disease pathways has been a common approach in the fight against AD. Unfortunately, most kinase inhibitors currently available target the adenosine triphosphate (ATP)- binding site, which has proven unsuccessful due to issues with selectivity and resistance. As a result, a pressing need to find other alternative sites beyond the ATP- binding site has profoundly evolved. In this review, we will showcase some case studies of inhibitors of tau protein kinases acting beyond ATP binding site which have shown promising results in alleviating AD.