| Autor: |
Mari Suzuki, Hiroshi Kuromi, Mayumi Shindo, Nozomi Sakata, Naoko Niimi, Koji Fukui, Minoru Saitoe, Kazunori Sango |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.09.22.509008 |
| Popis: |
SUMMARYDiabetic 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 exosome secretion 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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