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

• Published in: Molecular neurobiology 2023-03, Vol.60 (3), p.1690-1720
• Main Authors: Kaur, Preetpal, Khera, Alisha, Alajangi, Hema K., Sharma, Akanksha, Jaiswal, Pradeep K., Singh, Gurpal, Barnwal, Ravi P.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Cell Biology; Central nervous system; Clinical trials; Cyclin-dependent kinases; Cytosol; Drug delivery; Drug development; Enzymatic activity; Glycogen; Glycogen synthase kinase 3; Humans; Kinases; Microtubules; Nanotechnology; Neurobiology; Neurodegenerative diseases; Neurodegenerative Diseases - therapy; Neurofibrillary tangles; Neurology; Neurosciences; Phosphorylation; Proteins; Tau protein; tau Proteins - metabolism; Tauopathies - drug therapy; Tauopathies - metabolism
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-022-03164-z

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 (GSK3β) 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. Graphical Abstract Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.