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A small peptide mimetic of brain‐derived neurotrophic factor promotes peripheral myelination
Author(s) -
Xiao Junhua,
Hughes Richard A.,
Lim Joe Y.,
Wong Agnes W.,
Ivanusic Jason J.,
Ferner Anita H.,
Kilpatrick Trevor J.,
Murray Simon S.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12168
Subject(s) - tropomyosin receptor kinase b , neurotrophic factors , brain derived neurotrophic factor , neurotrophin , neuroscience , dorsal root ganglion , myelin , peripheral nervous system , biology , low affinity nerve growth factor receptor , myelin basic protein , in vitro , microbiology and biotechnology , receptor , central nervous system , biochemistry , spinal cord
The expression of the neurotrophins and their receptors is essential for peripheral nervous system development and myelination. We have previously demonstrated that brain‐derived neurotrophic factor (BDNF) exerts contrasting influences upon Schwann cell myelination in vitro – promoting myelination via neuronally expressed p75NTR, but inhibiting myelination via neuronally expressed TrkB. We have generated a small peptide called cyclo‐ d PAKKR that structurally mimics the region of BDNF that binds p75NTR. Here, we have investigated whether utilizing cyclo‐ d PAKKR to selectively target p75NTR is an approach that could exert a unified promyelinating response. Like BDNF, cyclo‐ d PAKKR promoted myelination of nerve growth factor‐dependent neurons in vitro , an effect dependent on the neuronal expression of p75NTR. Importantly, cyclo‐ d PAKKR also significantly promoted the myelination of tropomyosin‐related kinase receptor B‐expressing neurons in vitro , whereas BDNF exerted a significant inhibitory effect. This indicated that while BDNF exerted a contrasting influence upon the myelination of distinct subsets of dorsal root ganglion (DRG) neurons in vitro , cyclo‐ d PAKKR uniformly promoted their myelination. Local injection of cyclo‐ d PAKKR adjacent to the developing sciatic nerve in vivo significantly enhanced myelin protein expression and significantly increased the number of myelinated axons. These results demonstrate that cyclo‐ d PAKKR promotes peripheral myelination in vitro and in vivo , suggesting it is a strategy worthy of further investigation for the treatment of peripheral demyelinating diseases.