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A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease
Huntington’s disease (HD) is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and deme...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913682/ https://www.ncbi.nlm.nih.gov/pubmed/24503862 http://dx.doi.org/10.1371/journal.pone.0087923 |
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author | Todd, Daniel Gowers, Ian Dowler, Simon J. Wall, Michael D. McAllister, George Fischer, David F. Dijkstra, Sipke Fratantoni, Silvina A. van de Bospoort, Rhea Veenman-Koepke, Jessica Flynn, Geraldine Arjomand, Jamshid Dominguez, Celia Munoz-Sanjuan, Ignacio Wityak, John Bard, Jonathan A. |
author_facet | Todd, Daniel Gowers, Ian Dowler, Simon J. Wall, Michael D. McAllister, George Fischer, David F. Dijkstra, Sipke Fratantoni, Silvina A. van de Bospoort, Rhea Veenman-Koepke, Jessica Flynn, Geraldine Arjomand, Jamshid Dominguez, Celia Munoz-Sanjuan, Ignacio Wityak, John Bard, Jonathan A. |
author_sort | Todd, Daniel |
collection | PubMed |
description | Huntington’s disease (HD) is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF) is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB) receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models. |
format | Online Article Text |
id | pubmed-3913682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39136822014-02-06 A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease Todd, Daniel Gowers, Ian Dowler, Simon J. Wall, Michael D. McAllister, George Fischer, David F. Dijkstra, Sipke Fratantoni, Silvina A. van de Bospoort, Rhea Veenman-Koepke, Jessica Flynn, Geraldine Arjomand, Jamshid Dominguez, Celia Munoz-Sanjuan, Ignacio Wityak, John Bard, Jonathan A. PLoS One Research Article Huntington’s disease (HD) is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF) is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB) receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models. Public Library of Science 2014-02-04 /pmc/articles/PMC3913682/ /pubmed/24503862 http://dx.doi.org/10.1371/journal.pone.0087923 Text en © 2014 Todd et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Todd, Daniel Gowers, Ian Dowler, Simon J. Wall, Michael D. McAllister, George Fischer, David F. Dijkstra, Sipke Fratantoni, Silvina A. van de Bospoort, Rhea Veenman-Koepke, Jessica Flynn, Geraldine Arjomand, Jamshid Dominguez, Celia Munoz-Sanjuan, Ignacio Wityak, John Bard, Jonathan A. A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title | A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title_full | A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title_fullStr | A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title_full_unstemmed | A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title_short | A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease |
title_sort | monoclonal antibody trkb receptor agonist as a potential therapeutic for huntington’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913682/ https://www.ncbi.nlm.nih.gov/pubmed/24503862 http://dx.doi.org/10.1371/journal.pone.0087923 |
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