Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling
Identifieur interne : 000A88 ( Main/Exploration ); précédent : 000A87; suivant : 000A89Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling
Auteurs : Kristian L. Hedstrom ; Joshua C. Murtie ; Kathryn Albers ; Nigel A. Calcutt ; Gabriel CorfasSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
Small-fiber neuropathy (SFN) is a disorder of peripheral nerves that affects millions of people around the world. Currently, there are no treatments for SFN, but target-derived neurotrophic factors have been considered potential therapeutics. Here, we show that topical application of XIB4035, a small molecule that enhances signaling by the glial-derived neurotrophic factor family of molecules, ameliorates SFN pathologies and symptoms in two mouse models. These findings imply that XIB4035 or related molecules could provide a new strategy for SFN treatment with potentially lower risk for side effects because of the topical delivery route and their limited signaling effects.
Url:
DOI: 10.1073/pnas.1308889111
PubMed: 24449858
PubMed Central: 3926041
Affiliations:
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Kirby Neurobiology Center, Children’s Hospital Boston,<institution>Harvard Medical School</institution>, Boston,<addr-line>MA</addr-line> 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Albers, Kathryn" sort="Albers, Kathryn" uniqKey="Albers K" first="Kathryn" last="Albers">Kathryn Albers</name><affiliation><nlm:aff wicri:cut="; and" id="aff4">Department of Medicine,<institution>University of Pittsburgh School of Medicine</institution>, Pittsburgh,<addr-line>PA</addr-line> 15260</nlm:aff></affiliation></author><author><name sortKey="Calcutt, Nigel A" sort="Calcutt, Nigel A" uniqKey="Calcutt N" first="Nigel A." last="Calcutt">Nigel A. Calcutt</name><affiliation><nlm:aff id="aff5">Department of Pathology,<institution>University of California, San Diego</institution>, La Jolla,<addr-line>CA</addr-line> 92093-0612</nlm:aff></affiliation></author><author><name sortKey="Corfas, Gabriel" sort="Corfas, Gabriel" uniqKey="Corfas G" first="Gabriel" last="Corfas">Gabriel Corfas</name><affiliation><nlm:aff id="aff1">F. M. 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Hedstrom</name><affiliation><nlm:aff id="aff1">F. M. Kirby Neurobiology Center, Children’s Hospital Boston,<institution>Harvard Medical School</institution>, Boston,<addr-line>MA</addr-line> 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Murtie, Joshua C" sort="Murtie, Joshua C" uniqKey="Murtie J" first="Joshua C." last="Murtie">Joshua C. Murtie</name><affiliation><nlm:aff id="aff1">F. M. Kirby Neurobiology Center, Children’s Hospital Boston,<institution>Harvard Medical School</institution>, Boston,<addr-line>MA</addr-line> 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Albers, Kathryn" sort="Albers, Kathryn" uniqKey="Albers K" first="Kathryn" last="Albers">Kathryn Albers</name><affiliation><nlm:aff wicri:cut="; and" id="aff4">Department of Medicine,<institution>University of Pittsburgh School of Medicine</institution>, Pittsburgh,<addr-line>PA</addr-line> 15260</nlm:aff></affiliation></author><author><name sortKey="Calcutt, Nigel A" sort="Calcutt, Nigel A" uniqKey="Calcutt N" first="Nigel A." last="Calcutt">Nigel A. Calcutt</name><affiliation><nlm:aff id="aff5">Department of Pathology,<institution>University of California, San Diego</institution>, La Jolla,<addr-line>CA</addr-line> 92093-0612</nlm:aff></affiliation></author><author><name sortKey="Corfas, Gabriel" sort="Corfas, Gabriel" uniqKey="Corfas G" first="Gabriel" last="Corfas">Gabriel Corfas</name><affiliation><nlm:aff id="aff1">F. M. Kirby Neurobiology Center, Children’s Hospital Boston,<institution>Harvard Medical School</institution>, Boston,<addr-line>MA</addr-line> 02115;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Otology and Laryngology,<institution>Harvard Medical School</institution>, Boston,<addr-line>MA</addr-line> 02115;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Small-fiber neuropathy (SFN) is a disorder of peripheral nerves that affects millions of people around the world. Currently, there are no treatments for SFN, but target-derived neurotrophic factors have been considered potential therapeutics. Here, we show that topical application of XIB4035, a small molecule that enhances signaling by the glial-derived neurotrophic factor family of molecules, ameliorates SFN pathologies and symptoms in two mouse models. These findings imply that XIB4035 or related molecules could provide a new strategy for SFN treatment with potentially lower risk for side effects because of the topical delivery route and their limited signaling effects.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Albers, Kathryn" sort="Albers, Kathryn" uniqKey="Albers K" first="Kathryn" last="Albers">Kathryn Albers</name><name sortKey="Calcutt, Nigel A" sort="Calcutt, Nigel A" uniqKey="Calcutt N" first="Nigel A." last="Calcutt">Nigel A. Calcutt</name><name sortKey="Corfas, Gabriel" sort="Corfas, Gabriel" uniqKey="Corfas G" first="Gabriel" last="Corfas">Gabriel Corfas</name><name sortKey="Hedstrom, Kristian L" sort="Hedstrom, Kristian L" uniqKey="Hedstrom K" first="Kristian L." last="Hedstrom">Kristian L. Hedstrom</name><name sortKey="Murtie, Joshua C" sort="Murtie, Joshua C" uniqKey="Murtie J" first="Joshua C." last="Murtie">Joshua C. Murtie</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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