Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule
stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation
of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In
pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β),
cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated
kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation.
Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments
like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s
disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation.
We also discuss various strategies and the advancements made in the area of Alzheimer's
disease drug development by designing effective and specific inhibitors for such kinases using traditional
in vitro/in vivo methods and state of the art in silico techniques.
A current view on Tau protein phosphorylation in Alzheimer's disease
