Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies

J Med Chem. 2012 Nov 8;55(21):8979-96. doi: 10.1021/jm301079z. Epub 2012 Sep 28.

Abstract

The microtubule (MT) associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation, and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Axonal Transport
  • Biological Products / chemistry
  • Biological Products / therapeutic use
  • Blood-Brain Barrier / metabolism
  • Humans
  • Microtubules / drug effects
  • Microtubules / pathology
  • Molecular Targeted Therapy
  • Tauopathies / drug therapy*
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • tau Proteins / metabolism*

Substances

  • Biological Products
  • tau Proteins