Aptamer Antagonists of Myelin-Derived Inhibitors Promote Axon Growth 英文参考文献.docVIP

AptamerAntagonistsofMyelin-DerivedInhibitors PromoteAxonGrowth YuxuanWang1,ZinZ.Khaing2,NaLi1,BradHall1,ChristineE.Schmidt2,3,AndrewD.Ellington1* 1DepartmentofChemistryandBiochemistry,UniversityofTexasatAustin,Austin,Texas,UnitedStatesofAmerica,2DepartmentofBiomedicalEngineering,Universityof TexasatAustin,Austin,Texas,UnitedStates ofAmerica, 3Department ofChemicalEngineering,CockrellSchoolofEngineering,UniversityofTexasatAustin,Austin, Texas,UnitedStatesofAmerica Abstract Myelinoftheadultcentralnervoussystem(CNS)isoneofthemajorsourcesofinhibitorsofaxonregenerationfollowing injury.Thethreeknownmyelin-derivedinhibitors(Nogo,MAG,andOMgp)bindwithhighaffinitytotheNogo-66receptor (NgR)onaxonsandlimitneuriteoutgrowth.HereweshowthatRNAaptamerscanbegeneratedthatbindwithhighaffinity to NgR, compete with myelin-derived inhibitors for binding to NgR, and promote axon elongation of neurons in vitro even in the presence of these inhibitors. Aptamers may have key advantages over protein antagonists, including low immunogenicity and the possibility of ready modification during chemical synthesis for stability, signaling, or immobilization. This first demonstration that aptamers can directly influence neuronal function suggests that aptamers may prove useful for not only healing spinal cord and other neuronal damage, but may be more generally useful as neuromodulators. Citation: WangY,KhaingZZ,LiN,HallB,SchmidtCE,etal.(2010)Aptamer AntagonistsofMyelin-DerivedInhibitorsPromoteAxonGrowth.PLoSONE5(3): e9726.doi:10.1371/journal.pone.0009726 Editor:PetriKursula,UniversityofOulu,Germany ReceivedJuly9,2009;AcceptedFebruary22,2010;PublishedMarch16,2010 Copyright: ? 2010 Wang 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:ThisworkwasfundedinpartbytheNationalScienceFoundation,theHowardHughesMe