articleProceedings of the National Academy of SciencesJan 25, 2010GREEN OA

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

SJSung‐Wuk JangXLXia LiuMYManuel YepesKRKennie R. ShepherdGWGary W. Miller

Emory University · Georgia State University · +2 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

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…

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673
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Authors

11

Topics & keywords

Topics
Keywords
  • Tropomyosin receptor kinase B
  • Neurotrophic factors
  • Agonist
  • Neuroprotection
  • Brain-derived neurotrophic factor
  • Trk receptor
  • Pharmacology
  • Neurogenesis
UN Sustainable Development Goals
  • Good health and well-being
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