Perspective on Tau Hypothesis in Alzheimer’s Disease: Traversing the Therapeutic Potential of Flavonoids

Tau protein is found in abundance in brain. It is responsible for structural stabilization of neurons. It is a substrate of numerous protein kinases like glycogen synthase kinase-3 (GSK-3β), cyclin dependent protein kinase-5 (CDK5), and protein kinase A (PKA), which impel the deformation of its structure. In Alzheimer’s disease (AD), tau hyperphosphorylation entails the way to build-up neurofibrillary tangles (NFTs) inside the neurons. Lamentably, there are no such treatments that can reverse or halter the course of AD. The drugs approved by FDA, donepezil, galantamine, rivastigmine (cholinesterase inhibitors) and memantine (N-methyl D-aspartate receptors antagonists), provide only symptomatic relief from AD. An extensive literature survey from several databases like PubChem, Science Direct, and Web of Science was performed and it was concluded that naturally derived phytoconstituents can be a reliable alternative for AD treatment. The diverse spectrum of activity of the naturally occurring flavonoids may make them especially useful for preventing tau hyperphosphorylation by inhibiting the activity of various protein kinases like glycogen synthase kinase-3, cyclin-dependent protein kinase-5, and mitogen-activated protein kinases. The present review aims to identify the mechanisms of action and highlight the therapeutic benefits of different flavonoids in AD intervention.