Binding of Hsp90 to tau promotes a conformational change and aggregation of tau protein

J Alzheimers Dis. 2009;17(2):319-25. doi: 10.3233/JAD-2009-1049.


Tau pathology, associated with Alzheimer's disease, is characterized by the presence of phosphorylated and aggregated tau. Phosphorylation of tau takes place mainly in the vicinity of the tubulin-binding region of the molecule and its self aggregation is also mediated via this tubulin-binding region. Tau phosphorylation and aggregation have been related with conformational changes of the protein. These changes could be regulated by chaperones such as heat shock proteins, since one of these, heat shock protein 90 (Hsp90), has already been described as a putative tau-binding protein. In this work, we have confirmed the interaction of Hsp90 with tau protein and report that binding of Hsp90 to tau facilitates a conformational change that could result in its phosphorylation by glycogen synthase kinase 3 and its aggregation into filamentous structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysical Phenomena / physiology
  • Brain / metabolism
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • HSP90 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / ultrastructure
  • Humans
  • Immunoblotting / methods
  • Immunoprecipitation / methods
  • Microscopy, Electron, Scanning / methods
  • Phosphorylation
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Protein Conformation
  • Rats
  • tau Proteins / metabolism*
  • tau Proteins / ultrastructure


  • HSP90 Heat-Shock Proteins
  • tau Proteins
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3