PloS one, 2020-09, Vol.15 (9), p.e0239126
2020
Details
- Autor(en) / Beteiligte
- Titel
- PINK1 alleviates thermal hypersensitivity in a paclitaxel-induced Drosophila model of peripheral neuropathy
- Ist Teil von
- PloS one, 2020-09, Vol.15 (9), p.e0239126
- Ort / Verlag
- San Francisco: Public Library of Science
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- EZB Free E-Journals
- Beschreibungen/Notizen
- Paclitaxel is a representative anticancer drug that induces chemotherapy-induced peripheral neuropathy (CIPN), a common side effect that limits many anticancer chemotherapies. Although PINK1, a key mediator of mitochondrial quality control, has been shown to protect neuronal cells from various toxic treatments, the role of PINK1 in CIPN has not been investigated. Here, we examined the effect of PINK1 expression on CIPN using a recently established paclitaxel-induced peripheral neuropathy model in Drosophila larvae. We found that the class IV dendritic arborization (C4da) sensory neuron-specific expression of PINK1 significantly ameliorated the paclitaxel-induced thermal hyperalgesia phenotype. In contrast, knockdown of PINK1 resulted in an increase in thermal hypersensitivity, suggesting a critical role for PINK1 in sensory neuron-mediated thermal nociceptive sensitivity. Interestingly, analysis of the C4da neuron morphology suggests that PINK1 expression alleviates paclitaxel-induced thermal hypersensitivity by means other than preventing alterations in sensory dendrites in C4da neurons. We found that paclitaxel induces mitochondrial dysfunction in C4da neurons and that PINK1 expression suppressed the paclitaxel-induced increase in mitophagy in C4da neurons. These results suggest that PINK1 mitigates paclitaxel-induced sensory dendrite alterations and restores mitochondrial homeostasis in C4da neurons and that improvement in mitochondrial quality control could be a promising strategy for the treatment of CIPN.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0239126Titel-ID: cdi_plos_journals_2443876455
- Format
- –
- Schlagworte
- Anticancer properties, Biochemistry, Biology and Life Sciences, Cancer, Care and treatment, Causes of, Chemotherapy, Complications and side effects, Dendrites, Dendritic branching, Dendritic structure, Drosophila, Fruit flies, Health aspects, Homeostasis, Hypersensitivity, Insects, Kinases, Larvae, Medical research, Medical schools, Medicine, Medicine and Health Sciences, Mitochondria, Morphology, Neurons, Paclitaxel, Pain perception, Peripheral neuropathy, Phenotypes, Physiological aspects, Polyneuropathies, Protein kinases, PTEN-induced putative kinase, Quality control, Quality of life, Research and Analysis Methods, Sensory neurons, Side effects, Social Sciences, Supervision