A Drosophila model of diabetic neuropathy reveals a role of proteasome activity in the glia

Mari Suzuki, Hiroshi Kuromi, Mayumi Shindo, Nozomi Sakata, Naoko Niimi, Koji Fukui, Minoru Saitoe, Kazunori Sango

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetic peripheral neuropathy (DPN) is the most common chronic, progressive complication of diabetes mellitus. The main symptom is sensory loss; the molecular mechanisms are not fully understood. We found that Drosophila fed a high-sugar diet, which induces diabetes-like phenotypes, exhibit impairment of noxious heat avoidance. The impairment of heat avoidance was associated with shrinkage of the leg neurons expressing the Drosophila transient receptor potential channel Painless. Using a candidate genetic screening approach, we identified proteasome modulator 9 as one of the modulators of impairment of heat avoidance. We further showed that proteasome inhibition in the glia reversed the impairment of noxious heat avoidance, and heat-shock proteins and endolysosomal trafficking in the glia mediated the effect of proteasome inhibition. Our results establish Drosophila as a useful system for exploring molecular mechanisms of diet-induced peripheral neuropathy and propose that the glial proteasome is one of the candidate therapeutic targets for DPN.

Original languageEnglish
Article number106997
JournaliScience
Volume26
Issue number6
DOIs
Publication statusPublished - 2023 Jun 16

Keywords

  • Cell biology
  • Cellular physiology
  • Pathophysiology

ASJC Scopus subject areas

  • General

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