Table 1.
Summary of Drosophila CIPN studies.
| Study | Major findings in Drosophila | Translation to vertebrate models Evidence from the literature |
|---|---|---|
| Paclitaxel | ||
| Bhattacharya et al. (42) | ° Chronic treatment of paclitaxel induced nociceptive neuron degeneration ° Retinophilin knockdown prevented paclitaxel-induced degeneration in nociceptive neuron dendrites and axons and severed olfactory axons. ° Overexpression of Nmnat, but not p35, prevented paclitaxel-induced degeneration in nociceptive neurons |
°Subsequent experiments in embryonic mouse DRG culture demonstrated a conserved role of MORN4 in axonal degeneration following axotomy ° Retinophilin (MORN4) and Nmnat are conserved in mammals ° Nmnat in mammalian CIPN models showed protective effect |
| Brazill et al. (43) | °Acute treatment of paclitaxel induced dose-dependent hypersensitivity, hyperbranching, and perturbation to microtubule organization ° Overexpression of Nmnat prevented paclitaxel-induced hypersensitivity, but not hyperbranching or microtubule organization phenotypes |
°Nmnat in mammalian CIPN models showed protective effects |
| Kim et al. (68) | °PINK1 overexpression changed nociceptive neuron dendrite morphology and levels of PINK1 determined sensitivity to noxious stimuli ° PINK1 overexpression protected oxidative stress in mitochondria induced by paclitaxel |
°PINK1 is a conserved gene in mammals and showed protective effects in Parkinson's disease |
| Shin et al. (72) |
°Chronic treatment of paclitaxel induced dose-dependent nociceptive neuron degeneration, altered branching pattern, and hyposensitivity ° Paclitaxel perturbed trafficking of integrins, recycling endosomes and lysosomes ° Acute treatment of paclitaxel induced trafficking phenotypes prior to degeneration in nociceptive neurons ° Overexpression of integrins in nociceptors protected against selected paclitaxel-induced phenotypes |
° Paclitaxel reduced membrane recycling of integrins in mouse DRG neurons ° Paclitaxel perturbed motility of recycling endosomes and lysosome prior to degeneration in mouse DRG neurons ° Transduction of human ITGB1 in adult DRG neurons prevented degeneration in adult mouse DRG neurons ° Levels of integrins correlate with capacity of neuron regeneration after injury |
| Cisplatin | ||
| Podratz et al. (93) | °Acute cisplatin treatment induced dose-dependent lethality, reduced geotactic climbing behavior, cisplatin-DNA binding, and cellular apoptosis in brain, ovaries, but not in kidney and heart ° p35 overexpression prevented cisplatin-induced apoptosis in the brain and restored climbing behavior |
°Platinum-adduct levels found to be comparable to rat DRG neurons in their previous study |
| Podratz et al. (70) | °Acute treatment of cisplatin reduced mitochondrial activity, increased reactive oxygen species production and mitochondrial pausing° Cisplatin treatment resulted in behavioral deficiencies (heat sensing and righting) ° Overexpression of p35 prevented behavior and phenotypes |
° Mitochondria phenotypes are consistent with and complement the findings in mouse DRG neurons in their previous study |
| Groen et al. (66) | °Common background strains (Oregon-R, Canton-S, w1118) have different sensitivities to cisplatin in climbing behavior and survival rate ° ABC transporter mutants (relating to eye color mutants) have increased sensitivity to cisplatin |
°ABC transporters have been linked with cisplatin efficacy and multi-drug resistance |
| Groen et al. (67) | °Flies harboring attp40 insertion site have reduced ND-13A expression, a part of the mitochondria electron transport chain complex I° Neuron-specific ND-13A knockdown specifically prevents neuronal apoptosis (but not ovary cells), climbing deficiencies, and oxidative stress ° Protective capacity of ND-13A is Sirt-1 and PGC1-alpha dependent, and overexpression of Sirt-1 strongly prevented cisplatin phenotypes |
°SIRT1 activation protected sensory neurons from cisplatin-induced peripheral neuropathy in rodent models |
| Bortezomib | ||
| Pero et al. (69) | °Chronic treatment of bortezomib induced degeneration in nociceptive neurons° Acute treatment of bortezomib reduced catastrophe, rescue/nucleation frequencies and comet density by 3 h and reduced growth rate by 6 h | ° Bortezomib induced degeneration and acutely perturbed microtubule dynamics in cultured adult mouse DRG neurons ° Bortezomib promoted accumulation of hyperstable forms of tubulin (Delta 2) in rodent and human tissues |