特異結(jié)合APP上a分泌酶酶切位點(diǎn)單鏈抗體的篩選及其特性研究.pdf

1、寧夏大學(xué)碩士學(xué)位論文特異結(jié)合APP上a分泌酶酶切位點(diǎn)單鏈抗體的篩選及其特性研究姓名：張俊華申請(qǐng)學(xué)位級(jí)別：碩士專(zhuān)業(yè)：生物化學(xué)與分子生物學(xué)指導(dǎo)教師：王玉炯劉瑞田20090301AbstractAlzheimersdisease(AD)isacentralneuronalsystemdegenerativedisease，characterizedclinicallybymemoryloss，short—termmemory蛔u(yù)rycogni

2、tivedeclination，behaviorabnormityaswellaSlanguagedeficitsandpathologicallybyextraeellularsenileplaques(SP)，introcellularneurofibrillarytangles(NFT)andselectiveneuronallossAsawideacceptedtraitofAD，senileplaqueisgeneratedf

3、romtheextracelluardepositionofamyloid—betapeptide(AlB)，apathologicalproductderivedfromtheordinalcatalyzationofamyloid’precursorprotein(APP)bYI＆secretaseandv—secretase，thuscausingthec”ot0】【it)，andbrainfunctionobstacleWhil

4、einphysiologicalcircumstance，APPispronetobedigestedbyQsecrctaseataninnerA13siteproducingthe83residualtransmembraneCterminalfragment(C83)andaneuro—tonicandprotectiveN—terminalfragment(sAPPa)，whichcontributestomodulatesyna

5、pticplaSticityandsomehowinhibitsA13productionmakingthismetablisimpmhwayasignificanttargetforAnresearchandtherapya—seeretaseiscomposedofaseriesofmultifunctionalisoenzymesThedigestionmechanismon鼗Panditsrelationshipwiththeo

6、cculTenceanddevelopmentofADarestilltobewidelyinvestigatedanddiscussedUpuntilnowthereis，internationallynoeffectiveinhibitoronthedigestionofAPPbyasecretaseInfollowingworks，fourscFvsspecificallybindingasitewereobtainedafter

7、screeningofhumanscFvphagedisplaylibraryusingan0tsitecontiguoushexapeptideasantigenPositivecloneswereidentifiedbyPCRandsequencing，whilethebindingspecificityweretestedbyELISA，WesternblotandDotblotTheresultsdemonstratethatt

8、hepannedscFvCancombinewithAPPthesubstrateofn—secretase，andthusactasaninhibitorof伐一secretase，whichprovidesexperimentalmaterialfortheresearchanddiscussionoftbepathogenyofADKeywords：Alzheimer’Sdisease，B—amyloid，n—secretase，