资源描述：
《Ablation of P2X7 receptor》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、HumanMolecularGenetics,2013,Vol.22,No.204102–4116doi:10.1093/hmg/ddt259AdvanceAccesspublishedonJune4,2013AblationofP2X7receptorexacerbatesgliosisandmotoneurondeathintheSOD1-G93AmousemodelofamyotrophiclateralsclerosisSavinaApolloni1,2,SusannaAmadio2,CinziaMontilli2,CinziaVolonte´1,2andNadiaDA
2、mbrosi1,2,∗12CellularBiologyandNeurobiologyInstitute,CNR,Rome,ItalyandSantaLuciaFoundation,Rome,ItalyReceivedMarch28,2013;RevisedandAcceptedMay28,2013DownloadedfromAmyotrophiclateralsclerosis(ALS)isadevastatingneurologicaldisordercharacterizedbyselectivedegener-ationofupperandlowermotoneuron
3、s.Theprimarytriggersformotoneurondegenerationarestillunknown,butinflammationisconsideredanimportantcontributingfactor.P2X7receptorisakeyplayerinmicrogliaresponsetotoxicinsultsandwaspreviouslyshowntoincreasepro-inflammatoryactionsofSOD1-G93AALSmicroglia.http://hmg.oxfordjournals.org/Wetherefore
4、hypothesizedthatlackofP2X7receptorcouldmodifydiseasefeaturesintheSOD1-G93Amice.Hetero-andhomozygousP2X7receptorknock-outSOD1-G93Amicewerethusgeneratedandanalysedforbodyweight,diseaseonsetandprogression(bybehaviouralscores,gripandrotarodtests)andsurvival.1/22/2AlthoughthelifespanofP2X7andP2X7
5、/SOD1-G93Afemalemicewasextendedby67%withrespecttoSOD1-G93Amice,tooursurprisetheclinicalonsetwassignificantlyanticipatedandthediseaseprogression2/2worsenedinbothmaleandfemaleP2X7/SOD1-G93Amice.Consistently,wefoundincreasedastrogliosis,microgliosis,motoneuronloss,inductionofthepro-inflammatoryma
6、rkersNOX2andiNOSandactivationof2/2theMAPKspathwayinthelumbarspinalcordofend-stageP2X7/SOD1-G93Amice.TheseresultsshowatHefeiUniversityofTechnologyonJuly27,2014thattheconstitutivedeletionofP2X7receptoraggravatestheALSpathogenesis,suggestingthatthereceptormighthavebeneficialeffectsinatleastdefini
7、testagesofthedisease.ThisstudyunravelsacomplexdualroleofP2X7receptorinALSandstrengthenstheimportanceofasuccessfultimewindowoftherapeuticinterventionincontrastingthepathology.INTRODUCTIONappropriateanimalmodelsforALS(6).Althoughnumerouspathologicalp
