TrkB inhibition as a therapeutic target for CNS-related disorders

Fabien Boulle, Gunter Kenis*, Maxime Cazorla, Michel Hamon, Harry W. M. Steinbusch, Laurence Lanfumey, Daniel L. A. van den Hove

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The interaction of brain-derived neurotrophic factor ( BDNF) with its tropomyosin-related kinase receptor B (TrkB) is involved in fundamental cellular processes including neuronal proliferation, differentiation and survival as well as neurotransmitter release and synaptic plasticity. TrkB signaling has been widely associated with beneficial, trophic effects and many commonly used psychotropic drugs aim to increase BDNF levels in the brain. However, it is likely that a prolonged increased TrkB activation is observed in many pathological conditions, which may underlie the development and course of clinical symptoms. Interestingly, genetic and pharmacological studies aiming at decreasing TrkB activation in rodent models mimicking human pathology have demonstrated a promising therapeutic landscape for TrkB inhibitors in the treatment of various diseases, e.g. central nervous system (CNS) disorders and several types of cancer. Up to date, only a few selective and potent TrkB inhibitors have been developed. As such, the use of crystallography and in silico approaches to model BDNF-TrkB interaction and to generate relevant pharmacophores represent powerful tools to develop novel compounds targeting the TrkB receptor.
Original languageEnglish
Pages (from-to)197-206
JournalProgress in Neurobiology
Volume98
Issue number2
DOIs
Publication statusPublished - Aug 2012

Keywords

  • BDNF
  • Cancer
  • CNS disorders
  • TrkB inhibitors
  • Treatments

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