Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders

A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3 beta) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease.

Automated summary

Several protein kinases and phosphatases regulate tau protein phosphorylation, and an imbalance in their activity leads to tau hyper-phosphorylation. Aberrant tau phosphorylation causes it to dissociate from microtubules and form neurofibrillary tangles, contributing to neurodegenerative disorders. Restorative approaches targeting hyperphosphorylated tau protein are being explored, and drug delivery systems based on nanocarriers provide a potential solution for the limited transport of drugs to the central nervous system. This review discusses tau protein, regulation of its phosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the role of tau hyperphosphorylation in disease pathogenesis.