Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice.
In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the devel...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009777&type=printable |
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| author | Maxime Cazorla Anne Jouvenceau Christiane Rose Jean-Philippe Guilloux Catherine Pilon Alex Dranovsky Joël Prémont |
| author_facet | Maxime Cazorla Anne Jouvenceau Christiane Rose Jean-Philippe Guilloux Catherine Pilon Alex Dranovsky Joël Prémont |
| author_sort | Maxime Cazorla |
| collection | DOAJ |
| description | In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal) activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders. |
| format | Article |
| id | doaj-art-41adeacfb5c345d3bebdcfa44e95fb11 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-41adeacfb5c345d3bebdcfa44e95fb112025-08-20T03:19:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-03-0153e977710.1371/journal.pone.0009777Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice.Maxime CazorlaAnne JouvenceauChristiane RoseJean-Philippe GuillouxCatherine PilonAlex DranovskyJoël PrémontIn the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal) activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009777&type=printable |
| spellingShingle | Maxime Cazorla Anne Jouvenceau Christiane Rose Jean-Philippe Guilloux Catherine Pilon Alex Dranovsky Joël Prémont Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. PLoS ONE |
| title | Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. |
| title_full | Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. |
| title_fullStr | Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. |
| title_full_unstemmed | Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. |
| title_short | Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice. |
| title_sort | cyclotraxin b the first highly potent and selective trkb inhibitor has anxiolytic properties in mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009777&type=printable |
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