Recent developments with tau-based drug discovery

Expert Opin Drug Discov. 2018 May;13(5):399-410. doi: 10.1080/17460441.2018.1445084. Epub 2018 Mar 1.

Abstract

Alzheimer's disease (AD), which accounts for three fourth of all cases of dementia, is a major public health problem in modern society and, yet, there is no effective treatment available that can prevent or inhibit this chronic progressive neurodegenerative disease. A major current drug target is intraneuronal abnormally hyperphosphorylated microtubule-associated protein tau which is a histopathological hallmark of this disease and of a family of neurodegenerative diseases called tauopathies. Areas covered: In this review, the authors discuss a growing number of studies that describe the nature and mechanism of tau pathology and various drug discovery options and most recent developments in tau-based therapeutics. PubMed was used to obtain relevant literature while clinicaltrials.gov site and Google search were employed to obtain the latest information on tau based AD clinical trials. Expert opinion: In authors' opinion, loss of neuronal connectivity leads to the hyperphosphorylation of tau and is thus a key therapeutic target. Rescue of neuronal connectivity loss and hyperphosphorylation of tau are most promising approaches. Consequently, tau immunotherapy has a high therapeutic potential.

Keywords: Alzheimer’s disease; hyperphosphorylation of tau; microtubule-associated protein tau; neurogenesis; neuronal connectivity; neurotrophic support; synaptic plasticity; tauopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Disease Progression
  • Drug Discovery / methods*
  • Humans
  • Immunotherapy / methods
  • Phosphorylation / physiology
  • Tauopathies / drug therapy*
  • Tauopathies / physiopathology
  • tau Proteins / metabolism

Substances

  • tau Proteins