简介:Thequestforneuroprotectivedrugstoslowtheprogressionofneurodegenerativediseases(NDDs),includingAlzheimer'sdisease(AD),Parkinson'sdisease(PD),andHuntington'sdisease(HD),hasbeenlargelyunrewarding.Preclinicalevidencesuggeststhatrepurposingquetiapine,lithium,valproate,fluoxetine,donepezil,andmemantineforearlyandpre-symptomaticdisease-modificationinNDDsmaybepromisingandcanspareregulatorybarriers.Theliteratureofthesepsychotropicsinearlystageandpre-symptomaticAD,PD,andHDisreviewedandpropitiousfindingsfollow.Mildcognitiveimpairment(MCI)phaseofAD:salutaryhumanrandomizedcontrolledtrialfindingsforlow-doselithiumand,inselectedpatients,donepezilawaitreplication.Pre-symptomaticAD:humanepidemiologicaldataindicatethatlithiumreducesADrisk.Animalmodelstudies(AMS)revealencouragingresultsforquetiapine,lithium,donepezil,andmemantine.EarlyPD:valproateAMSfindingsshowpromise.Pre-symptomaticPD:lithiumandvalproateAMSfindingsareencouraging.EarlyHD:uncontrolledclinicaldataindicatenon-progressionwithlithium,fluoxetine,donepezil,andmemantine.Pre-symptomaticHD:lithiumandvalproateareauspiciousinAMS.Manyotherpromisingfindingsawaitingreplication(valproateinMCI;lithium,valproate,fluoxetineinpre-symptomaticAD;lithiuminearlyPD;lithium,valproate,fluoxetineinpre-symptomaticPD;donepezilinearlyHD;lithium,fluoxetine,memantineinpre-symptomaticHD)arereviewed.Dose-andstage-dependenteffectsareconsidered.Suggestionsforsignal-enhancementinhumantrialsareprovidedforeachNDDstage.
简介:Neurotrophicfactorscompriseessentialsecretedproteinsthathaveseveralfunctionsinneuralandnon-neuraltissues,mediatingthedevelopment,survivalandmaintenanceofperipheralandcentralnervoussystem.Therefore,neurotrophicfactorissuehasbeenextensivelyinvestigatedintothecontextofneurodegenerativediseases.Alzheimer'sdiseaseandParkinson'sdiseaseshowchangesintheregulationofspecificneurotrophicfactorsandtheirreceptors,whichappeartobecriticalforneuronaldegeneration.Indeed,neurotrophicfactorspreventcelldeathindegenerativeprocessesandcanenhancethegrowthandfunctionofaffectedneuronsinthesedisorders.Basedonrecentreports,thisreviewdiscussesthemainfindingsrelatedtotheneurotrophicfactorsupport–mainlybrain-derivedneurotrophicfactorandglialcellline-derivedneurotrophicfactor–inthesurvival,proliferationandmaturationofaffectedneuronsinAlzheimer'sdiseaseandParkinson'sdiseaseaswellastheirputativeapplicationasnewtherapeuticapproachforthesediseasesmanagement.
简介:BACKGROUND:Itisdifficulttoattractinterestinnon-compulsory,preventive,medicalcare,andpersonsdiagnosedwithcertaindiseasesoftenignoretheexistenceofthesediseases.However,Huntington'sdisease(HD)isanexception.OBJECTIVE:ToqualitativelyanalyzefactorsmotivatingHDpatientstoparticipateinastudy,namelytheEuropeanHuntington'sDiseaseNetwork(EHDN)REGISTRY.DESIGN,TIMEANDSETTING:AnobservationalsurveywasconductedintheEHDNStudySiteinPoznan,Polandbetween2007and2008.PARTICIPANTS:Thestudyinvolved22personsaffectedwithHDand3pre-symptomaticindividuals,totaling9malesand16females.The24participantsinthisstudyhad24differentcaregivers.Atotalof25symptomaticorpre-symptomaticsubjectsparticipatedintheinitialREGISTRYvisit,aswellas6inthesecond,and1inthethird.Allsubjectsdidnotknoweachotherpriortothevisit.METHODS:AmutationintheIT15genewasconfirmedineachpatientorpre-symptomaticmutationcarrier.Anin-depthinterviewproduceddetailedinformationontheHDpatients,aswellasthecaregivers,fortheREGISTRYstudy.MAINOUTCOMEMEASURES:AqualitativeanalysisofthefactorsmotivatingHDpatientsandthepre-symptomaticmutationcarrierstoparticipateintheREGISTRYlongitudinal,observational,researchprojectwasperformed.RESULTS:TheprimarymotivatingfactorforinvolvementofHDpatientsandthecaregiversintheREGISTRYstudywasthehopethataneffectiveHDtherapywouldsoonbediscovered.InHDpatientsandthepre-symptomaticgroup,theresponsetoparticipateintheREGISTRYprojectreached100%,despitethefactthattheyknewtheprojectwasonlyanobservationalstudy.CONCLUSION:Patienthopeisthoughttobeafactorforengaginginpreventive,therapeuticactivities.However,thisisrarelymentionedinmedicalpapersandclinicaltextbooks,andisusuallyoverlookedinmedicalteaching.Clearly,effortsshouldbemadetoincludethisinclinicalpractice.
简介:Parkinsonsdisease(PD)isacommon,progressiveneurodegenerativediseasecharacterisedbydegenerationofnigrostriataldopaminergicneurons,aggregationofα-synucleinandmotorsymptoms.Currentdopamine-replacementstrategiesprovidesymptomaticrelief,howevertheireffectivenesswearoffovertimeandtheirprolongeduseleadstodisablingside-effectsinPDpatients.ThereisthereforeacriticalneedtodevelopnewdrugsanddrugtargetstoprotectdopaminergicneuronsandtheiraxonsfromdegenerationinPD.Overrecentyears,therehasbeenrobustevidencegeneratedshowingthatepigeneticdysregulationoccursinPDpatients,andthatepigeneticmodulationisapromisingtherapeuticapproachforPD.Thisarticlefirstdiscussesthepresentevidenceimplicatingglobal,anddopaminergicneuron-specific,alterationsinthemethylomeinPD,andthetherapeuticpotentialofpharmacologicallytargetingthemethylome.Itthenfocusesonanothermechanismofepigeneticregulation,histoneacetylation,anddescribeshowthehistoneacetyltransferase(HAT)andhistonedeacetylase(HDAC)enzymesthatmediatethisprocessareattractivetherapeutictargetsforPD.Itdiscussestheuseofactivatorsand/orinhibitorsofHDACsandHATsinmodelsofPD,andhowtheseapproachesfortheselectivemodulationofhistoneacetylationelicitneuroprotectiveeffects.Finally,itoutlinesthepotentialofemployingsmallmoleculeepigeneticmodulatorsasneuroprotectivetherapiesforPD,andthefutureresearchthatwillberequiredtodetermineandrealisethistherapeuticpotential.
简介:Propofolcaninhibittheinflammatoryresponseandreducethesecretionandharmfuleffectsofastrocyte-derivedproinflammatorycytokines.Inthisstudy,afterpropofolwasinjectedintotheinjuredsciaticnerveofmice,nuclearfactorkappaBexpressionintheL4-6segmentsofthespinalcordintheinjuredsidewasreduced,apoptosiswasdecreased,nervemyelindefectswerealleviated,andthenerveconductionblockwaslessened.Theexperimentalfindingsindicatethatpropofolinhibitstheinflammatoryandimmuneresponses,decreasestheexpressionofnuclearfactorkappaB,andreducesapoptosis.Theseeffectsofpropofolpromoteregenerationfollowingsciaticnerveinjury.
简介:BACKGROUND:ToevaluatethequalityoftheliteratureaddressingtraditionalChinesemedicinefortreatingParkinson'sdisease.DATASOURCE:Acomputer-basedonlinesearchofChinesepublicationsfromJanuary2001toJuly2008wasconductedinChineseBiologyMedicalDiscDatabaseandChinaNationalKnowledgeInfrastructure.SearchkeywordswereParkinson'sdisease,integratedtraditionalChineseandWesternmedicine,traditionalChinesemedicinetherapy,andChineseherbtherapy.DATASELECTION:Articlesdescribingrandomized,controlledtrialsandquasi-randomized,controlledtrialswereincluded.Literaturequalitywasassessedusingthecriteria-SystematicevaluationofclinicalliteraturerelatedtotreatmentofParkinson'sdiseasewithtraditionalChinesemedicine.Thisincludedmethodology,interventionsinthetreatment/controlgroup,evaluationcriterionofoutcomes,andfrequency.MAINOUTCOMEMEASURES:Evaluationcriterionofoutcomes(variousscoremethodsandevaluationscales),methodologicalquality,andfrequencydistributionwereallmeasured.RESULTS:Atotalof33articleswithrandomized,controlledtrialswereincluded.Ofthese,sixdescribedarandommethod,andtheremainingdidnotdescriberandomallocationmethodsorrandomsequencegenerationmethods.Noneofthestudiesestimatedsamplesize.Casedescriptionsofwithdrawalandlosstofollow-upwereunclear.BoththeUnifiedParkinson'sDiseaseRatingScaleandWebsterscalewereusedintheeligiblestudiesasevaluationcriteria.CONCLUSION:Therearenohigh-qualitystudiesthataddresstraditionalChinesemedicinetherapyandintegratedtraditionalChineseandWesternmedicinefortreatingParkinson'sdiseaseinChina.EligiblestudieswerenotperformedinaccordancewithConsolidatedStandardsofReportingTrialsstatementorStandardsforReportingInterventionsinControlledTrialsofAcupuncturecriteria,andtheliteraturequalitywaslow.ThepresentlyusedcriteriaforevaluatingtherapeuticeffectsdonotcompletelyassessoutcomesoftraditionalCh
简介:Parkinson’sdisease(PD)isanage-relatedneurodegenerativedisordercharacterizedbytypicalmotorsignsandsymptomsthatareduetodopamine(DA)depletioninthebasalganglia.ThetreatmentofPDissymptomatic,andaimsatreplacingthelostDAinputusingeitherL-DOPAorDAagonists.ThecausesofPDareunknownin
简介:SubthalamicnucleusdeepbrainstimulationhasbecomeastandardneurosurgicaltherapyforadvancedParkinson’sdisease.Subthalamicnucleusdeepbrainstimulationcandramaticallyimprovethemotorsymptomsofcarefullyselectedpatientswiththisdisease.Surprisingly,somespecificdimensionsofqualityoflife,"psychological"aspectsandsocialadjustmentdonotalwaysimprove,andtheycouldsometimesbeevenworse.Patientsandtheirfamiliesshouldfullyunderstandthatsubthalamicnucleusdeepbrainstimulationcanalterthemotorstatusandtimeisneededtoreadapttotheirnewpostoperativestateandlifestyles.Thispaperreviewstheliteraturesregardingeffectsofbilateralsubthalamicnucleusdeepbrainstimulationonsocialadjustment,qualityoflifeandcopingstrategiesinpatientswithParkinson’sdisease.ThefindingsmayhelptounderstandthepsychosocialmaladjustmentandpoorimprovementinqualityoflifeinsomeParkinson’sdiseasepatients.
简介:Genisteiniseffectiveagainstamyloid-βtoxicity,buttheunderlyingmechanismsareunclear.Wehypothesizedthatgenisteinmayprotectneuronsbyinhibitingthemitochondrialapoptoticpathway,andtherebyplayaroleinthepreventionofAlzheimer'sdisease.AratmodelofAlzheimer'sdiseasewasestablishedbyintraperitonealinjectionofD-galactoseandintracerebralinjectionofamyloid-βpeptide(25–35).Inthegenisteintreatmentgroups,a7-daypretreatmentwithgenistein(10,30,90mg/kg)wasgivenpriortoestablishingAlzheimer'sdiseasemodel,for49consecutivedays.Terminaldeoxyribonucleotidyltransferase-mediateddUTPnickendlabelingassaydemonstratedareductioninapoptosisinthehippocampusofratstreatedwithgenistein.Westernblotanalysisshowedthatexpressionlevelsofcapase-3,Baxandcytochromecweredecreasedcomparedwiththemodelgroup.Furthermore,immunohistochemicalstainingrevealedreductionsincytochromecandBaximmunoreactivityintheserats.MorriswatermazerevealedasubstantialshorteningofescapelatencybygenisteininAlzheimer'sdiseaserats.Thesefindingssuggestthatgenisteindecreasesneuronallossinthehippocampus,andimproveslearningandmemoryability.Theneuroprotectiveeffectsofgenisteinareassociatedwiththeinhibitionofthemitochondrialapoptoticpathway,asshownbyitsabilitytoreducelevelsofcaspase-3,Baxandcytochromec.