Gender- and Age-Dependent γ-Secretase Activity in Mouse Brain and Its Implication in Sporadic Alzheimer Disease 英文参考文献.docVIP
- 1、本文档共9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
查看更多
Gender- and Age-Dependent γ-Secretase Activity in Mouse Brain and Its Implication in Sporadic Alzheimer Disease 英文参考文献
Gender-andAge-Dependentc-SecretaseActivityin
MouseBrainandItsImplicationinSporadicAlzheimer
Disease
LisaPlacanica1,2,LeiZhu1,Yue-MingLi1,2*
1Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America, 2Department of
Pharmacology,WeillGraduateSchoolofMedicalSciencesofCornellUniversity,NewYork,NewYork,UnitedStatesofAmerica
Abstract
Alzheimerdisease(AD)isanage-relateddisorder.Agingandfemalegenderaretwoimportantriskfactorsassociatedwith
sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is
unclear.Itiswellknownthatgeneticmutationsinc-secretaseresultinrareformsofearlyonsetADduetotheaberrant
productionofAb42peptides,whicharethemajorconstituentsofsenileplaques.However,theeffectofageandgenderon
c-secretasehasnotbeenfullyinvestigated.Here,usingnormalwild-typemice,weshowmousebrainc-secretaseexhibits
gender-andage-dependentactivity.BothmaleandfemalemiceexhibitincreasedAb42:Ab40ratiosinagedbrain,which
mimicstheeffectoffamilialmutations ofPresenilin-1,Presenlin-2,andtheamyloidprecursorproteinonAbproduction.
Additionally,femalemiceexhibitmuchhigherc-secretaseactivityinagedbraincomparedtomalemice.Furthermore,both
maleand femalemice exhibit asteady decline in Notch1 c-secretase activitywith aging. Usingasmall molecule affinity
probewedemonstratethatmalemicehavelessactivec-secretasecomplexesthanfemalemice,whichmayaccountforthe
gender-associateddifferencesinactivityinagedbrain.Thesefindingsdemonstratethatagingcanaffectc-secretaseactivity
andspecificity,suggestingaroleforc-secretaseinsporadicAD.Furthermore,theincreasedAPPc-secretaseactivityseenin
agedfemalesmaycontributetotheincreasedincidenceofsporadicADinwomenandtheaggressiveAbplaquepathology
seen in female mouse models of AD. In addition, deceased Notch c-secretase activity may also contribute to
neurodegeneration.Therefore,thisstudyimplicatesalteredc-secretaseactivityandspecificityasapossiblemechan
您可能关注的文档
- Functional Polymorphism of the Mu-Opioid Receptor Gene (OPRM1) Influences Reinforcement Learning in Humans 英文参考文献.doc
- Functional Neurokinin and NMDA Receptor Activity in an Animal Naturally Lacking Substance P The Naked Mole-Rat 英文参考文献.doc
- Functional Overlap between eIF4G Isoforms in Saccharomyces cerevisiae 英文参考文献.doc
- Functional Maps of Human Auditory Cortex Effects of Acoustic Features and Attention 英文参考文献.doc
- Functional Interactions between the eruptedtsg101 Growth Suppressor Gene and the DaPKC and rbf1 Genes in Drosophila Imaginal Disc Tumors 英文参考文献.doc
- Functional PstIRsaI Polymorphism in CYP2E1 Is Associated with the Development, Progression and Poor Outcome of Gastric Cancer 英文参考文献.doc
- Functional Polymorphisms in the TERT Promoter Are Associated with Risk of Serous Epithelial Ovarian and Breast Cancers 英文参考文献.doc
- Functional Polymorphisms in PRODH Are Associated with Risk and Protection for Schizophrenia and Fronto-Striatal Structure and Function 英文参考文献.doc
- Functional Mutation of Multiple Solvent-Exposed Loops in the Ecballium elaterium Trypsin Inhibitor-II Cystine Knot Miniprotein 英文参考文献.doc
- Functional Polymorphism -31CG in the Promoter of BIRC5 Gene and Risk of Nasopharyngeal Carcinoma among Chinese 英文参考文献.doc
文档评论(0)