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D-β-hydroxybutyrate is protective in mouse models of Huntington's disease

DC Field Value Language
dc.contributor.author임소연-
dc.date.accessioned2018-05-10T06:32:46Z-
dc.date.available2018-05-10T06:32:46Z-
dc.date.issued2011-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/158163-
dc.description.abstractAbnormalities in mitochondrial function and epigenetic regulation are thought to be instrumental in Huntington's disease (HD), a fatal genetic disorder caused by an expanded polyglutamine track in the protein huntingtin. Given the lack of effective therapies for HD, we sought to assess the neuroprotective properties of the mitochondrial energizing ketone body, D-β-hydroxybutyrate (DβHB), in the 3-nitropropionic acid (3-NP) toxic and the R6/2 genetic model of HD. In mice treated with 3-NP, a complex II inhibitor, infusion of DβHB attenuates motor deficits, striatal lesions, and microgliosis in this model of toxin induced-striatal neurodegeneration. In transgenic R6/2 mice, infusion of DβHB extends life span, attenuates motor deficits, and prevents striatal histone deacetylation. In PC12 cells with inducible expression of mutant huntingtin protein, we further demonstrate that DβHB prevents histone deacetylation via a mechanism independent of its mitochondrial effects and independent of histone deacetylase inhibition. These pre-clinical findings suggest that by simultaneously targeting the mitochondrial and the epigenetic abnormalities associated with mutant huntingtin, DβHB may be a valuable therapeutic agent for HD.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherPublic Library of Science-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESH3-Hydroxybutyric Acid/therapeutic use*-
dc.subject.MESHAcetylation/drug effects-
dc.subject.MESHAnimals-
dc.subject.MESHHistones/metabolism-
dc.subject.MESHHuntington Disease/drug therapy*-
dc.subject.MESHImmunoblotting-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHNitro Compounds/therapeutic use-
dc.subject.MESHPC12 Cells-
dc.subject.MESHPropionates/therapeutic use-
dc.subject.MESHRats-
dc.titleD-β-hydroxybutyrate is protective in mouse models of Huntington's disease-
dc.typeArticle-
dc.contributor.collegeResearch Institutes-
dc.contributor.departmentYonsei Integrative Research Institute for Cerebral & Cardiovascular Disease-
dc.contributor.googleauthorSoyeon Lim-
dc.contributor.googleauthorAdrianne S. Chesser-
dc.contributor.googleauthorJonathan C. Grima-
dc.contributor.googleauthorPhillip M. Rappold-
dc.contributor.googleauthorDavid Blum-
dc.contributor.googleauthorSerge Przedborski-
dc.contributor.googleauthorKim Tieu-
dc.identifier.doi10.1371/journal.pone.0024620-
dc.contributor.localIdA03373-1-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid21931779-
dc.contributor.alternativeNameLim, So Yeon-
dc.contributor.affiliatedAuthorLim, So Yeon-
dc.citation.volume6-
dc.citation.number9-
dc.citation.startPagee24620-
dc.identifier.bibliographicCitationPLOS ONE, Vol.6(9) : e24620, 2011-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers

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