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1、StrategizingtheDevelopmentofAlzheimer’sTherapeuticsStrategizingtheDevelopmentofAlzheimer’sTherapeuticsJustinDavis,RobinCouchDepartmentofChemistryandBiochemistry,GeorgeMasonUniversity,Manassas,VA,USAEmail:rcouchgmu.eduReceived10June2014;revised25July2014;accepted5August2014C
2、opyright©2014byauthorsandScientificResearchPublishingInc.ThisonsAttributionInternationalLicense(CCBY).creativemons.org/licenses/by/4.0/AbstractAlzheimer’sDiseaseisaplex,progressiveconditionptomsthatdonotrevealthemselvesuntilsignificantchangestoneuronalmorphologyhavealr
3、eadyoccurred.Thedelayedmanifestationofcognitivedeclinemakesdeterminationofthetrueetiologicaloriginsdifficult.Asaresult,identificationofidealdrugtargetsbeesseeminglyimpossible.TheexistingtreatmentsforAlzheimer’sDiseasemaytemporarilysuppresstherateofcognitivedecline,butdolitt
4、letosloanybelievethatthecurrentapproachestoidentifyingacureforthediseasearetoonarroinded,focusingheavilyonthephysicalmanifestationsofthediseasedbrainsuchasamyloidplaquesandneurofibrillarytangles,thisrevieer’sresearchasrationalandmulti-faceted.Keyer’sDisease,TargetIdentifica
5、tion,Therapeutics,Revieer’sDisease(AD),themostmonformofdementia,involvestheprogressivedeteriorationofcognitiveandfunctionalabilities,ultimatelyleadingtothelossofbodilyfunctionanddeath.Accordingtothe[15])thatinhibitsbothacetylcholinesteraseandbutyrylcholinesteraseilaraffinit
6、y[17].RivastigmineremainsboundtotheenzymeforagreateramountoftimethantheotherAChEinhibitors(10hoursversusminutesfordonepezil)[18],asitscarbamatemoietyremainsboundintheesteraticsiteoftheenzymefolloinegeneratesimprovementsincognitivefunctionatlog/dayandhighdosesof6-12mg/day.Ho
7、entsinglobalassessmentsalsocorrelateilarefficacyinregardstocognitivefunction,behavior,andglobaloute[14].Meta-analysisperformedbyHansenetal.in2008[19]proposesagreaterbehavioralresponseforpatientstreatedentine,althoughthedifferencesareminute.Overall,thethreeacetylcholinestera
8、seinhibitorstemporarilystabilizetherateofbehavioral,cognitive,andfunctionaldecline