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Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy.


ABSTRACT: 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.

SUBMITTER: Brazill JM 

PROVIDER: S-EPMC6031360 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Nmnat mitigates sensory dysfunction in a <i>Drosophila</i> model of paclitaxel-induced peripheral neuropathy.

Brazill Jennifer M JM   Cruz Beverley B   Zhu Yi Y   Zhai R Grace RG   Zhai R Grace RG  

Disease models & mechanisms 20180612 6


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 <i>in vivo</i> mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using <i>Drosophila</i> larvae that recapitulates aspects o  ...[more]

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