TrkB Agonist LM22A-4 Increases Oligodendroglial Populations During Myelin Repair in the Corpus Callosum

Huynh T.H. Nguyen, Rhiannon J. Wood, Alexa R. Prawdiuk, Sebastian G.B. Furness, Junhua Xiao, Simon S. Murray, Jessica L. Fletcher

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23 Citations (Scopus)


The neurotrophin, brain-derived neurotrophic factor (BDNF) promotes central nervous system (CNS) myelination during development and after injury. This is achieved via activation of oligodendrocyte-expressed tropomyosin-related kinase (Trk) B receptors. However, while administration of BDNF has shown beneficial effects, BDNF itself has a poor pharmacokinetic profile. Here, we compare two TrkB-targeted BDNF-mimetics, the structural-mimetic, tricyclic dimeric peptide-6 (TDP6) and the non-peptide small molecule TrkB agonist LM22A-4 in a cuprizone model of central demyelination in female mice. Both mimetics promoted remyelination, increasing myelin sheath thickness and oligodendrocyte densities after 1-week recovery. Importantly, LM22A-4 exerts these effects in an oligodendroglial TrkB-dependent manner. However, analysis of TrkB signaling by LM22A-4 suggests rather than direct activation of TrkB, LM22A-4 exerts its effects via indirect transactivation of Trk receptors. Overall, these studies support the therapeutic strategy to selectively targeting TrkB activation to promote remyelination in the brain.

Original languageEnglish
Article number205
Number of pages12
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 27 Aug 2019


  • BDNF
  • myelin
  • neurotrophin
  • oligodendrocytes
  • remyelination
  • TrkB

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