Development of tau aggregation inhibitors for Alzheimer's disease

Angew Chem Int Ed Engl. 2009;48(10):1740-52. doi: 10.1002/anie.200802621.


A variety of human diseases are suspected to be directly linked to protein misfolding. Highly organized protein aggregates, called amyloid fibrils, and aggregation intermediates are observed; these are considered to be mediators of cellular toxicity and thus attract a great deal of attention from investigators. Neurodegenerative pathologies such as Alzheimer's disease account for a major part of these protein misfolding diseases. The last decade has witnessed a renaissance of interest in inhibitors of tau aggregation as potential disease-modifying drugs for Alzheimer's disease and other "tauopathies". The recent report of a phase II clinical trial with the tau aggregation inhibitor MTC could hold promise for the validation of the concept. This Review summarizes the available data concerning small-molecule inhibitors of tau aggregation from a medicinal chemistry point of view.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Amyloid / antagonists & inhibitors
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Benzothiazoles
  • Databases, Factual
  • Humans
  • Tauopathies / drug therapy
  • Thiazoles / metabolism
  • tau Proteins / antagonists & inhibitors*
  • tau Proteins / metabolism


  • Amyloid
  • Amyloid beta-Peptides
  • Benzothiazoles
  • Thiazoles
  • tau Proteins
  • thioflavin T