气候变化领域集成服务门户(CCPortal): Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy

CCPortal

DOI	10.1073/pnas.2006050118
	Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy
	Shin G.J.-E.; Pero M.E.; Hammond L.A.; Burgos A.; Kumar A.; Galindo S.E.; Lucas T.; Bartolini F.; Grueber W.B.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin β-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cell surface proteins; CIPN; Drosophila; Integrins; Neuropathy
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179886
作者单位	Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, Columbia University, New York, NY 10027, United States; Pathology & Cell Biology, Columbia University, New York, NY 10032, United States; Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, 80137, Italy; Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, United States; Neuroscience, Columbia University, New York, NY 10027, United States
推荐引用方式 GB/T 7714	Shin G.J.-E.,Pero M.E.,Hammond L.A.,et al. Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy[J],2021,118(15).
APA	Shin G.J.-E..,Pero M.E..,Hammond L.A..,Burgos A..,Kumar A..,...&Grueber W.B..(2021).Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Shin G.J.-E.,et al."Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).