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

Jennifer M. Brazill, Beverley Cruz, Yi Zhu, R. Grace Zhai

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article numberdmm.032938
JournalDMM Disease Models and Mechanisms
Volume11
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • Chemotherapy
  • Microtubules
  • Neuropathy
  • Neuroprotection
  • Nmnat
  • Paclitaxel

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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