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.

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简介：AbstractThe main treatments for Parkinson’s disease (PD) currently include surgery, rehabilitation, and most commonly, drug therapy. However, the drugs that are currently used to treat PD provide only symptomatic relief and delayed disease progression but have no curative effect and cause many adverse reactions. When considering pathogenic factors and metabolic regulation, PD and type 2 diabetes have a high rate of comorbidity; this provides a theoretical basis for the treatment of PD with first-line antidiabetic drugs. Among these agents, metformin reduces neuronal damage in the brains of PD patients via neuroprotection and the inhibition of oxidative stress and inflammatory responses, thus providing a novel strategy for the clinical treatment of PD. Here, we present the current state of knowledge about the use of metformin to treat PD and discuss its clinical prospects.

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简介：AbstractBackground:The prevalence rates of freezing of gait (FOG) in Parkinson’s disease (PD) vary widely, ranging from 14.0 to 55.1%. Our aim is to calculate the overall prevalence of FOG in all PD patients with different disease durations and severities.Methods:Using Medline/PubMed/Embase, we carried out a systematic literature search for studies reporting the PD and clinically relevant FOG.Results:After primary screening, a total of 35 studies were identified and further analyzed for inclusion into the analysis, and 29 studies fulfilled the quality criteria and included in this meta-analysis. The overall prevalence of FOG in PD was 39.9% (95% CI 35.3-44.5%). The FOG identified by the freezing of gait questionnaire item 3 may be more prevalent (43.8%, 95% CI 38.5-49.1%) than the FOG identified by the Unified Parkinson’s Disease Rating Scale item 14 (36.0%, 95% CI 29.0-43.1%). Disease duration and severity are both the clinical features associated with the FOG. The highest FOG prevalence rate in PD patients was seen in patients with disease durations ≥ 10 years, at 70.8%, followed that of PD patients with disease durations ≥ 5 years (53.3%), and PD patients with disease durations < 5 years (22.4%). FOG presented in 28.4% of PD patients with Hoehn and Yahr staging (H&Y) score ≤ 2.5, and in 68.4% of PD patients with H&Y score ≥ 2.5.Conclusion:This meta-analysis confirms that the prevalence of FOG in PD is considerable, and highlights the need for accurate identification of FOG in PD.

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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：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：Background:Manydisease-specificfactorssuchasmuscularweakness,increasedmusclestiffness,varyingposturalstrategies,andchangesinposturalreflexeshavebeenshowntoleadtoposturalinstabilityandfallriskinpeoplewithParkinson'sdisease(PD).Recently,analyticaltechniques,inspiredbythedynamicalsystemsperspectiveonmovementcontrolandcoordination,havebeenusedtoexaminethemechanismsunderlyingthedynamicsofposturaldeclinesandtheemergenceofposturalinstabilitiesinpeoplewithPD.Methods:Awavelet-basedtechniquewasusedtoidentifylimitcycleoscillations(LCOs)intheanterior–posterior(AP)posturalswayofpeoplewithmildPD(n=10)comparedtoage-matchedcontrols(n=10).Participantsstoodonafoamandonarigidsurfacewhilecompletingadualtask(speaking).Results:Therewasnosignificantdifferenceintherootmeansquareofcenterofpressurebetweengroups.Threeoutof10participantswithPDdemonstratedLCOsonthefoamsurface,whilenoneinthecontrolgroupdemonstratedLCOs.AninvertedpendulummodelofbipedalstancewasusedtodemonstratethatLCOsoccurduetodisease-specificchangesassociatedwithPD:time-delayandneuromuscularfeedbackgain.Conclusion:Overall,theLCOanalysisandmathematicalmodelappeartocapturethesubtleposturalinstabilitiesassociatedwithmildPD.Inaddition,thesefindingsprovideinsightsintothemechanismsthatleadtotheemergenceofunstablepostureinpatientswithPD.

简介：AbstractBackground:The antioxidant effects of bilirubin in Parkinson’s disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD.Methods:Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software.Results:A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050-0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102-0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: -0.223, 95% CI: -0.952-0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324-0.698, P = 0.000, I2 = 58.0%).Conclusion:Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.

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简介：AIM:ToevaluatetheeffectofOcimumsanctumleafextractonthedietarysupplementationinthetransgenicDrosophilamodelofParkinson’sdisease.METHOD:TheeffectofOcimumsanctumleafextractwasstudiedonthetransgenicDrosophilamodeloffliesexpressingnormalhumanalphasynuclein(h-αs)intheneurons.O.sanctumextractatfinalconcentrationsof0.0428×10-4,0.87×10-4,and1.85×10-4g·mL-1ofdietwereestablishedandtheflieswereallowedtofeedfor21days.Theclimbingassayandlipidperoxidationweretakenasparametersforthestudy.RESULTS:ThesupplementationofO.sanctumextractshowedadose-dependentsignificantdelayinthelossofclimbingabilityandreductioninoxidativestressinthebrainofPDmodelflies.CONCLUSION:TheresultsofthepresentstudyshowedthattheO.sanctumextractispotentinreducingthePDsymptomsintransgenicDrosophilamodel.

简介：Overthepastdecade,nineseparategenetherapyclinicaltrialsforadvancedParkinson’sdisease(PD)havebeenlaunchedandcompleted,involvingthedosingofnearly12-dozenPDvolunteerswhoincurredsignificantriskstohopefullyreducesymptomsand

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