Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A
Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral ner...
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2021-11-01
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| author | Na-Young Park Geon Kwak Hyun-Myung Doo Hye-Jin Kim So-Young Jang Yun-Il Lee Byung-Ok Choi Young-Bin Hong |
| author_facet | Na-Young Park Geon Kwak Hyun-Myung Doo Hye-Jin Kim So-Young Jang Yun-Il Lee Byung-Ok Choi Young-Bin Hong |
| author_sort | Na-Young Park |
| collection | DOAJ |
| description | Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by <i>PMP22</i> overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT. |
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| issn | 1467-3037 1467-3045 |
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| last_indexed | 2024-03-10T04:23:31Z |
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| spelling | doaj.art-0d05dcbda8e348daa3bf9ee143eff9432023-11-23T07:44:12ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-11-014332011202110.3390/cimb43030138Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1ANa-Young Park0Geon Kwak1Hyun-Myung Doo2Hye-Jin Kim3So-Young Jang4Yun-Il Lee5Byung-Ok Choi6Young-Bin Hong7Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, KoreaDepartments of Biochemistry, College of Medicine, Dong-A University, Busan 49201, KoreaWell Aging Research Center, Division of Biotechnology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, KoreaDepartment of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, KoreaCharcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by <i>PMP22</i> overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.https://www.mdpi.com/1467-3045/43/3/138Charcot-Marie-Tooth disease (CMT)farnesolmyelination |
| spellingShingle | Na-Young Park Geon Kwak Hyun-Myung Doo Hye-Jin Kim So-Young Jang Yun-Il Lee Byung-Ok Choi Young-Bin Hong Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A Current Issues in Molecular Biology Charcot-Marie-Tooth disease (CMT) farnesol myelination |
| title | Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A |
| title_full | Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A |
| title_fullStr | Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A |
| title_full_unstemmed | Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A |
| title_short | Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A |
| title_sort | farnesol ameliorates demyelinating phenotype in a cellular and animal model of charcot marie tooth disease type 1a |
| topic | Charcot-Marie-Tooth disease (CMT) farnesol myelination |
| url | https://www.mdpi.com/1467-3045/43/3/138 |
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