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Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031360/ https://www.ncbi.nlm.nih.gov/pubmed/29716954 http://dx.doi.org/10.1242/dmm.032938 |
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author | Brazill, Jennifer M. Cruz, Beverley Zhu, Yi Zhai, R. Grace |
author_facet | Brazill, Jennifer M. Cruz, Beverley Zhu, Yi Zhai, R. Grace |
author_sort | Brazill, Jennifer M. |
collection | PubMed |
description | Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using Drosophila larvae that recapitulates aspects of chemotherapy-induced sensory dysfunction. We showed that nociceptive sensitivity is associated with disrupted organization of microtubule-associated MAP1B/Futsch and aberrant stabilization of peripheral sensory dendrites. These findings establish a robust and amenable model for studying peripheral mechanisms of CIPN. Using this model, we uncovered a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons and uncovered Nmnat's therapeutic potential against diverse sensory symptoms of CIPN. |
format | Online Article Text |
id | pubmed-6031360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60313602018-07-06 Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy Brazill, Jennifer M. Cruz, Beverley Zhu, Yi Zhai, R. Grace Dis Model Mech Research Article Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using Drosophila larvae that recapitulates aspects of chemotherapy-induced sensory dysfunction. We showed that nociceptive sensitivity is associated with disrupted organization of microtubule-associated MAP1B/Futsch and aberrant stabilization of peripheral sensory dendrites. These findings establish a robust and amenable model for studying peripheral mechanisms of CIPN. Using this model, we uncovered a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons and uncovered Nmnat's therapeutic potential against diverse sensory symptoms of CIPN. The Company of Biologists Ltd 2018-06-01 2018-06-12 /pmc/articles/PMC6031360/ /pubmed/29716954 http://dx.doi.org/10.1242/dmm.032938 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Brazill, Jennifer M. Cruz, Beverley Zhu, Yi Zhai, R. Grace Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title | Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title_full | Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title_fullStr | Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title_full_unstemmed | Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title_short | Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy |
title_sort | nmnat mitigates sensory dysfunction in a drosophila model of paclitaxel-induced peripheral neuropathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031360/ https://www.ncbi.nlm.nih.gov/pubmed/29716954 http://dx.doi.org/10.1242/dmm.032938 |
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