Computational modelling of kinase inhibitors as anti-alzheimer agents

Abstract

Alzheimer’s disease is one of the leading causes of deaths in both developed as well as developing countries. It is characterized mainly by the deposition of extracellular β-amyloid plaques and intracellular neurofibrillary tangles. To date various hypotheses regarding the aetiology of AD have been reported in the literature, but the exact cause of AD still remains unknown. Hyperphosphorylation of tau protein is considered as one of the most accepted reasons by the scientists and researchers throughout the world. Currently, four FDA-approved drugs (rivastigmine, galantamine, donepezil, memantine) are available in the market, and the fifth one (tacrine) is withdrawn due its hepatotoxicity concerns. Protein kinases are well-known targets in cancer, and several reports are available regarding their critical role in the hyperphosphorylation of tau protein in AD. Although not even a single molecule is available in the market for the treatment of AD as a kinase inhibitor, a number of studies are in the pipeline targeting the kinases. In this chapter efforts have been made to discuss the computational studies carried out till date on various protein kinases in search of potential anti-Alzheimer’s agents.