气候变化领域集成服务门户(CCPortal): Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy

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DOI	10.1073/pnas.2012685118
	Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy
	Pero M.E.; Meregalli C.; Qu X.; Shin G.J.-E.; Kumar A.; Shorey M.; Rolls M.M.; Tanji K.; Brannagan T.H.; Alberti P.; Fumagalli G.; Monza L.; Grueber W.B.; Cavaletti G.; Bartolini F.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	The pathogenesis of chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood. Here, we report that the CIPN-causing drug bortezomib (Bort) promotes delta 2 tubulin (D2) accumulation while affecting microtubule stability and dynamics in sensory neurons in vitro and in vivo and that the accumulation of D2 is predominant in unmyelinated fibers and a hallmark of bortezomib-induced peripheral neuropathy (BIPN) in humans. Furthermore, while D2 overexpression was sufficient to cause axonopathy and inhibit mitochondria motility, reduction of D2 levels alleviated both axonal degeneration and the loss of mitochondria motility induced by Bort. Together, our data demonstrate that Bort, a compound structurally unrelated to tubulin poisons, affects the tubulin cytoskeleton in sensory neurons in vitro, in vivo, and in human tissue, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. The results reveal a previously unrecognized pathogenic role for D2 in BIPN that may occur through altered regulation of mitochondria motility. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Axonopathy; Bortezomib; Delta 2 tubulin; DRG; Mitochondria
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/180890
作者单位	Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, United States; Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, 80137, Italy; Experimental Neurology Unit, School of Medicine and Surgery and NeuroMI (Milan Center for Neuroscience), University of Milano-Bicocca, Monza, 20900, Italy; Department of Physiology and Cellular Biophysics, Zuckerman Mind Brain and Behavior Institute, Jerome L. Greene Science Center, Columbia University, New York, NY 10027, United States; Department of Neuroscience, Zuckerman Mind Brain and Behavior Institute, Jerome L. Greene Science Center, Columbia University, New York, NY 10027, United States; Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, United States; Department of Neurology, Columbia University Medical Center, New York, NY 10032, United States
推荐引用方式 GB/T 7714	Pero M.E.,Meregalli C.,Qu X.,et al. Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy[J],2021,118(4).
APA	Pero M.E..,Meregalli C..,Qu X..,Shin G.J.-E..,Kumar A..,...&Bartolini F..(2021).Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Pero M.E.,et al."Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).