Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases

Nat Rev Drug Discov. 2007 Jun;6(6):464-79. doi: 10.1038/nrd2111.

Abstract

Aggregation of hyperphosphorylated tau is one of the characteristic neuropathological lesions of Alzheimer's disease and other neurodegenerative disorders. Pharmacological modulation of tau hyperphosphorylation might represent a valid and feasible therapeutic strategy for such disorders. Here, we consider recent evidence supporting the validity of the three most relevant kinases affecting tau hyperphosphorylation - GSK3beta, CDK5 and ERK2 - as drug targets and describe progress in the design of inhibitors for these kinases.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Brain / metabolism
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 5 / chemistry
  • Drug Design*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / chemistry
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / chemistry
  • Neurodegenerative Diseases / drug therapy*
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • tau Proteins / metabolism*

Substances

  • Protein Kinase Inhibitors
  • tau Proteins
  • Cyclin-Dependent Kinase 5
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Mitogen-Activated Protein Kinase 1
  • Glycogen Synthase Kinase 3