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TrkB agonist LM22A-4 increases oligodendroglial populations during myelin repair in the corpus callosum

Citation

Nguyen, HTH and Wood, RJ and Prawdiuk, AR and Furness, SGB and Xiao, J and Murray, SS and Fletcher, JL, TrkB agonist LM22A-4 increases oligodendroglial populations during myelin repair in the corpus callosum, Frontiers in Molecular Neuroscience pp. 1-12. ISSN 1662-5099 (2019) [Refereed Article]


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Copyright Statement

Copyright 2019 Nguyen, Wood, Prawdiuk, Furness, Xiao, Murray and Fletcher. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fnmol.2019.00205

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 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.

Item Details

Item Type:Refereed Article
Keywords:oligodendrocyte, myelin, BDNF, multiple sclerosis, demyelinating disease, animal models
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Fletcher, JL (Dr Jessica Fletcher)
ID Code:147222
Year Published:2019
Web of Science® Times Cited:8
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-19
Last Modified:2021-11-03
Downloads:2 View Download Statistics

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