气候变化领域集成服务门户(CCPortal): Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model

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DOI	10.1073/PNAS.1922392117
	Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model
	Lohr K.M.; Frost B.; Scherzer C.; Feany M.B.
发表日期	2021
ISSN	00278424
起始页码	33608
结束页码	33618
卷号	117 期号:52
英文摘要	Mitochondrial and metabolic dysfunction are often implicated in neurological disease, but effective mechanism-based therapies remain elusive. We performed a genome-scale forward genetic screen in a Drosophila model of tauopathy, a class of neurodegenerative disorders characterized by the accumulation of the protein tau, and identified manipulation of the B-vitamin biotin as a potential therapeutic approach in tauopathy. We show that tau transgenic flies have an innate biotin deficiency due to tau-mediated relaxation of chromatin and consequent aberrant expression of multiple biotin-related genes, disrupting both carboxylase and mitochondrial function. Biotin depletion alone causes mitochondrial pathology and neurodegeneration in both flies and human neurons, implicating mitochondrial dysfunction as a mechanism in biotin deficiency. Finally, carboxylase biotin levels are reduced in mammalian tauopathies, including brains of human Alzheimer’s disease patients. These results provide insight into pathogenic mechanisms of human biotin deficiency, the resulting effects on neuronal health, and a potential therapeutic pathway in the treatment of tau-mediated neurotoxicity. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Biotin; Drosophila; Mitochondria; Screen; Tau
语种	英语
scopus关键词	biotin; neurotoxin; Alzheimer disease; animal; biotinylation; brain; disease model; Drosophila melanogaster; drug effect; female; gene expression regulation; genetic screening; genetics; human; male; metabolism; mitochondrion; mouse; nerve cell; nerve degeneration; pathology; physiology; tauopathy; transgenic animal; Alzheimer Disease; Animals; Animals, Genetically Modified; Biotin; Biotinylation; Brain; Disease Models, Animal; Drosophila melanogaster; Female; Gene Expression Regulation; Genetic Testing; Humans; Male; Mice; Mitochondria; Nerve Degeneration; Neurons; Neurotoxins; Tauopathies
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/179656
作者单位	Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States; Department of Biology, Washington and Jefferson College, Washington, PA 15301, United States; Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States; Neurogenomics Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Lohr K.M.,Frost B.,Scherzer C.,et al. Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model[J],2021,117(52).
APA	Lohr K.M.,Frost B.,Scherzer C.,&Feany M.B..(2021).Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Lohr K.M.,et al."Biotin rescues mitochondrial dysfunction and neurotoxicity in a tauopathy model".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).