Journal article

The TrkB agonist LM22A-4 increases oligodendroglial populations and remyelination in the brain

SS Murray, HTH Nguyen, RJ Wood, AR Prawdiuk, J Xiao, JL Fletcher

MULTIPLE SCLEROSIS JOURNAL | SAGE PUBLICATIONS LTD | Published : 2020

Abstract

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 the cuprizone model of central demyelination in female mice. Both mimetics promoted remyelination, increasing myelin sheath thickness and oligodendrocyte densities..

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University of Melbourne Researchers