Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration 英文参考文献.docVIP

Oxr1IsEssentialforProtectionagainstOxidativeStress- InducedNeurodegeneration PeterL.Oliver1.,Matte′aJ.Finelli1.,BenjaminEdwards1,EmmanuelleBitoun1,DarcyL.Butts1,EstherB.E. Becker1,MichaelT.Cheeseman2,BenDavies3,KayE.Davies1* 1Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom, 2Medical ResearchCouncilHarwell,Harwell,UnitedKingdom,3WellcomeTrustCentreforHumanGenetics,Oxford,UnitedKingdom Abstract Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over- expressed.AconservedshortisoformofOxr1isalsosufficienttoconferthisneuroprotectivepropertybothinvitroandin vivo.Inaddition,biochemicalassaysindicatethatOxr1itselfissusceptibletocysteine-mediatedoxidation.Finallyweshow up-regulationofOxr1inbothhumanandpre-symptomaticmousemodelsofamyotrophiclateralsclerosis,indicatingthat Oxr1ispotentiallyanovelneuroprotectivefactorinneurodegenerativedisease. Citation: Oliver PL, Finelli MJ, Edwards B, Bitoun E, Butts DL, et al. (2011) Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration.PLoSGenet7(10):e1002338.doi:10.1371/journal.pgen.1002338 Editor:HarryT.Orr,UniversityofMinnesota,UnitedStatesofAmerica ReceivedMay18,2011;AcceptedAugust24,2011;PublishedOctober20,2011 Copyright: ? 2011 Oliver et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This research was funded