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PINK1 alleviates thermal hypersensitivity in a paclitaxel-induced Drosophila model of peripheral neuropathy

Title
PINK1 alleviates thermal hypersensitivity in a paclitaxel-induced Drosophila model of peripheral neuropathy
Authors
Kim, Young YeonYoon, Jeong-HyunUm, Jee-HyunJeong, Dae JinShin, Dong JinHong, Young BinKim, Jong KukKim, Dong HyunKim, ChangsooChung, Chang GeonLee, Sung BaeKoh, HyongjongYun, Jeanho
DGIST Authors
Kim, Young Yeon; Yoon, Jeong-Hyun; Um, Jee-Hyun; Jeong, Dae Jin; Shin, Dong Jin; Hong, Young Bin; Kim, Jong Kuk; Kim, Dong Hyun; Kim, Changsoo; Chung, Chang Geon; Lee, Sung Bae; Koh, Hyongjong; Yun, Jeanho
Issue Date
2020-09
Citation
PLoS ONE, 15(9), e0239126
Type
Article
Article Type
Article
Keywords
OXIDATIVE STRESSMITOCHONDRIAL DYSFUNCTIONINDUCED APOPTOSISALPHA-SYNUCLEINMITOPHAGYNEURONS
ISSN
1932-6203
Abstract
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. © 2020 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI
http://hdl.handle.net/20.500.11750/12433
DOI
10.1371/journal.pone.0239126
Publisher
Public Library of Science
Related Researcher
  • Author Lee, Sung Bae Laboratory of Neurodegenerative Diseases and Aging
  • Research Interests Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles


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