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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-06-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/11/6/dmm032938 |
| _version_ | 1811263597682098176 |
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| author | Jennifer M. Brazill Beverley Cruz Yi Zhu R. Grace Zhai |
| author_facet | Jennifer M. Brazill Beverley Cruz Yi Zhu R. Grace Zhai |
| author_sort | Jennifer M. Brazill |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T19:47:06Z |
| format | Article |
| id | doaj.art-fd37a69f926642f6854c451057b20c7f |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-12T19:47:06Z |
| publishDate | 2018-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-fd37a69f926642f6854c451057b20c7f2022-12-22T03:18:55ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-06-0111610.1242/dmm.032938032938Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathyJennifer M. Brazill0Beverley Cruz1Yi Zhu2R. Grace Zhai3 Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA 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.http://dmm.biologists.org/content/11/6/dmm032938PaclitaxelChemotherapyNeuropathyMicrotubulesNmnatNeuroprotection |
| spellingShingle | Jennifer M. Brazill Beverley Cruz Yi Zhu R. Grace Zhai Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy Disease Models & Mechanisms Paclitaxel Chemotherapy Neuropathy Microtubules Nmnat Neuroprotection |
| 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 | Paclitaxel Chemotherapy Neuropathy Microtubules Nmnat Neuroprotection |
| url | http://dmm.biologists.org/content/11/6/dmm032938 |
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