A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone

Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2687-92. doi: 10.1073/pnas.0913572107. Epub 2010 Jan 25.


Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cells, Cultured
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Phosphorylation / drug effects
  • Protein Multimerization / drug effects
  • Receptor, trkB / agonists*
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Signal Transduction / drug effects


  • 6,7-dihydroxyflavone
  • Brain-Derived Neurotrophic Factor
  • Flavones
  • Neuroprotective Agents
  • Receptor, trkB