Gamma-Secretase Represents a Therapeutic Target for the Treatment of Invasive Glioma Mediated by the p75 Neurotrophin Receptor 英文参考文献.docVIP

下载本文档

3
0
约8.98万字
约 16页
2017-05-11 发布于上海
举报
版权申诉

Gamma-Secretase Represents a Therapeutic Target for the Treatment of Invasive Glioma Mediated by the p75 Neurotrophin Receptor 英文参考文献.doc

1、本文档共16页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Gamma-Secretase Represents a Therapeutic Target for the Treatment of Invasive Glioma Mediated by the p75 Neurotrophin Receptor 英文参考文献

o PL SBIOLOGY Gamma-SecretaseRepresentsaTherapeutic TargetfortheTreatmentofInvasiveGlioma Mediatedbythep75NeurotrophinReceptor LiMei Wang1,2,3,Jennifer J.Rahn1,2,3,XueQing Lun1,3,Beichen Sun1,3,John J.P.Kelly4,5,Samuel Weiss4,5 Stephen M.Robbins1,2,3,Peter A.Forsyth1,2,3,6[*,Donna L.Senger1,3[* , 1DepartmentofOncology,UniversityofCalgary,andTomBakerCancerCentre,Calgary,Canada,2DepartmentofBiochemistryandMolecularBiology,UniversityofCalgary, Calgary, Canada, 3 Clark H. Smith Brain Tumor Center and Southern Alberta Cancer Research Institute, Calgary, Canada, 4 Department of Cell Biology and Anatomy, UniversityofCalgary,Calgary,Canada,5HotchkissBrainInstitute,Calgary,Canada,6DepartmentofClinicalNeurosciences,UniversityofCalgary,Calgary,Canada Themultifunctionalsignalingproteinp75neurotrophinreceptor(p75NTR)isacentralregulatorandmajorcontributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembraneproteolysis(RIP)ofp75NTR isrequiredforp75NTR-mediatedgliomainvasion,andidentifyapreviously unnamed process for targeted glioma therapy. Expression of cleavage-resistant chimeras of p75NTR or treatment of animals bearing p75NTR-positive intracranial tumors with clinically applicable c-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival. Importantly, proteolytic processing of p75NTR was observed in p75NTR-positive patient tumor specimens and brain tumor initiating cells. This work highlights the importanceofp75NTRasatherapeutictarget,suggestingthatc-secretaseinhibitorsmayhavedirectclinicalapplication forthetreatmentofmalignantglioma. Citation:WangL,RahnJJ,LunX,SunB,KellyJJP,etal.(2008)Gamma-secretaserepresentsatherapeutictargetforthetreatmentofinvasivegliomamediatedbythep75 neurotrophinreceptor.PLoSBiol6(11):e289.doi:10.1371/journal.pbio.0060289 group was found to strongly correlate with poor patient survival.Ourunderstandingoftheproteinsthatinitiate,and Introduc