气候变化领域集成服务门户(CCPortal): Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice

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DOI	10.1126/science.aaz8899
	Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice
	Guthrie L.M.; Soma S.; Yuan S.; Silva A.; Zulkifli M.; Snavely T.C.; Greene H.F.; Nunez E.; Lynch B.; de Ville C.; Shanbhag V.; Lopez F.R.; Acharya A.; Petris M.J.; Kim B.-E.; Gohil V.M.; Sacchettini J.C.
发表日期	2020
ISSN	0036-8075
起始页码	620
结束页码	625
卷号	368 期号:6491
英文摘要	Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse—a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	copper copper zinc superoxide dismutase cytochrome c oxidase dopamine beta monooxygenase elesclomol monophenol monooxygenase protein lysine 6 oxidase copper cytochrome c oxidase elesclomol hydrazine derivative copper cytochrome enzyme enzyme activity mitochondrion mortality mutation pathology rodent survival animal cell animal experiment animal model animal tissue Article cohort analysis controlled study disease severity drug mechanism Golgi complex H9c2(2-1) cell line in vivo study male Menkes syndrome mitochondrial dynamics mortality rate mouse nerve degeneration nonhuman priority journal secretory pathway survival rate animal brain cell line degenerative disease disease model drug effect genetics knockout mouse Menkes syndrome metabolism mitochondrion pathology rat transport at the cellular level Murinae Mus Animals Biological Transport Brain Cell Line Copper Copper Transporter 1 Disease Models, Animal Electron Transport Complex IV Hydrazines Male Menkes Kinky Hair Syndrome Mice Mice, Knockout Mitochondria Neurodegenerative Diseases Rats
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133511
推荐引用方式 GB/T 7714	Guthrie L.M.,Soma S.,Yuan S.,et al. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice[J]. Science,2020,368(6491).
APA	Guthrie L.M..,Soma S..,Yuan S..,Silva A..,Zulkifli M..,...&Sacchettini J.C..(2020).Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice.,368(6491).
MLA	Guthrie L.M.,et al."Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice".368.6491(2020).