气候变化领域集成服务门户(CCPortal): Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation

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DOI	10.1073/pnas.2017225118
	Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation
	Giovinazzo D.; Bursac B.; Sbodio J.I.; Nalluru S.; Vignane T.; Snowman A.M.; Albacarys L.M.; Sedlak T.W.; Torregrossa R.; Whiteman M.; Filipovic M.R.; Snyder S.H.; Paul B.D.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	Alzheimer’s disease (AD), the most common cause of dementia and neurodegeneration in the elderly, is characterized by deterioration of memory and executive and motor functions. Neuropathologic hallmarks of AD include neurofibrillary tangles (NFTs), paired helical filaments, and amyloid plaques. Mutations in the microtubule-associated protein Tau, a major component of the NFTs, cause its hyperphosphorylation in AD. We have shown that signaling by the gaseous molecule hydrogen sulfide (H2S) is dysregulated during aging. H2S signals via a posttranslational modification termed sulfhydration/persulfidation, which participates in diverse cellular processes. Here we show that cystathionine γ-lyase (CSE), the biosynthetic enzyme for H2S, binds wild type Tau, which enhances its catalytic activity. By contrast, CSE fails to bind Tau P301L, a mutant that is present in the 3xTg-AD mouse model of AD. We further show that CSE is depleted in 3xTg-AD mice as well as in human AD brains, and that H2S prevents hyperphosphorylation of Tau by sulfhydrating its kinase, glycogen synthase kinase 3β (GSK3β). Finally, we demonstrate that sulfhydration is diminished in AD, while administering the H2S donor sodium GYY4137 (NaGYY) to 3xTg-AD mice ameliorates motor and cognitive deficits in AD. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alzheimer’s disease; GSK3beta; Hydrogen sulfide; Sulfhydration; Tau
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/180924
作者单位	Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Leibniz-Institut für Analytische Wissenschaften–ISAS–e.V., Dortmund, 44227, Germany; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; University of Exeter Medical School, Exeter, EX1 2LU, United Kingdom; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
推荐引用方式 GB/T 7714	Giovinazzo D.,Bursac B.,Sbodio J.I.,等. Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation[J],2021,118(4).
APA	Giovinazzo D..,Bursac B..,Sbodio J.I..,Nalluru S..,Vignane T..,...&Paul B.D..(2021).Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Giovinazzo D.,et al."Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).