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简介：Humanrhodopsinkinase(RK)andacarboxylterminus-truncatedmutantRKlackingthelast59aminoacids(RKC)wereexpressedinhumanembryonickidney293cellstoinvestigatetheroleofthecarboxylterminusofRKinrecognitionandphosphorylationofrhodopsin.RKC,likethewild-typeRK,wasdetectedinbothplasmamembranesandcytosolicfractions.TheCterminaltruncatedrhodopsinkinasewasunabletophosphorylatephoto-activatedrhodopsin,butpossesseskinaseactivitysimilartothewild-typeRKinphosphorylationofsmallpeptidesubstrate.ItsuggeststhatthetruncationdidnotdisturbthegrossstructuresofRKcatalyticdomain.OurresultsalsoshowthatRKCfailedtotranslocatetophoto-activatedrodoutsegments.Takentogether,ourstudydemonstratethecarboxylterminusofRKisrequiredforphosphorylationofphoto-activatedrhodopsinandstronglyindicatethatcarboxyl-terminusofRKmaybeinvolvedininteractionwithphoto-activatedrhodopsin.

简介：Ourpreviousstudiesshowedapredominanceofhighmolecularweightproteingroupintumornuclearmatrices.Contrarytonormalcells,proteinsofthisgrouparepreferentiallyphosphorylated.Phosphoproteinsofhepatomanuclearmatrixareselectivelysubjectedtorapidproteolysis.Byalkalitreatmentandamonoclonalantibodyagainstphosphotyrosylresiduethepresenceoftwohighmolecularweightbandsofphosphotyrosyl-containingproteinswasdetectedinnuclearmatricesoftumorbutnotofnormallivercells.Highmolecularweightproteingroupoftumornuclearmatricesrevealedalsoarapidturnoverandpreferentialincorporationoflabeledaminoacidsselectivelyinhibitedbychloramphenicol.

简介：增加的证据证明丝氨酸，threonine和酷氨酸残余上的蛋白质phosphorylation是在细菌的主要规章的translational以后修正。这评论在细菌的致病力集中于细菌的phosphoproteome的含意并且在phosphoproteomics和phosphorylation网络的连接加亮方法的最近的开发。在高精确性团spectrometry的最近的技术开发戏剧性地转变了proteomics并且使它可能一些彻底的地点特定的细菌的phosphoproteomes的描述。在一些细菌的phosphoproteomes的高许多酷氨酸phosphorylations在致病力建议他们的角色，特别在病原体主人相互作用的情况中；在细菌的邻蛋白质的高许多multi-phosphorylation地点是相对小的phosphorylation尺寸和蛋白质功能的精细的规定的指示物的赔偿。

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简介：Alzheimer型老年痴呆(Alzheimer'sdisease,AD)是一种常见的老年异质性脑神经退行性疾病,以不可逆进行性记忆和认知功能丧失为主要临床特征,是老年人痴呆的主要原因.AD发病机理极其复杂,属多病因、多阶段的慢性中枢神经疾病,至今AD的发病机制尚未完全阐明.Alzheimer型痴呆的主要神经病理特征包括:神经细胞内的神经元纤维缠结(NFT);神经细胞外的神经变性斑,又称老年斑(SP),其核心主要是β-淀粉样肽Aβ的沉积;还有大量神经细胞的凋亡丧失等.而与NFT发生有密切关系的神经蛋白是tau蛋白(τ蛋白),可以认为异常磷酸化及糖基化修饰tau蛋白的病理性沉积最终导致NFT的形成.

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简介：MaleWistar7-day-oldratswereinjectedwith40mg/kgketamineintraperitoneally,followedbythreeadditionalinjectionsof20mg/kgketamineeachuponrestorationoftherightingreflex.Neonatalratsinjectedwithequivalentvolumesofsalineservedascontrols.Hippocampalsampleswerecollectedat1,7or14daysfollowingadministration.Electronmicroscopyshowedthatneuronalstructurechangednoticeablyfollowingketaminetreatment.Specifically,microtubularstructurebecameirregularanddisorganized.Quantitativerealtime-PCRrevealedthatphosphorylatedtaumRNAwasupregulatedafterketamine.Westernblotanalysisdemonstratedthatphosphorylatedtaulevelsatserine396initiallydecreasedat1dayafterketamineinjection,andthengraduallyreturnedtocontrolvalues.At14daysafterinjection,levelsofphosphorylatedtauwerehigherintheketaminegroupthaninthecontrolgroup.Tauproteinphosphorylatedatserine404significantlyincreasedafterketamineinjection,andthengraduallydecreasedwithtime.However,thelevelsoftauproteinatserine404weresignificantlygreaterintheketaminegroupthaninthecontrolgroupuntil14days.ThepresentresultsindicatethatketamineinducesanincreaseofphosphorylatedtaumRNAandexcessivephosphorylationoftauproteinatserine404,causingdisruptionofmicrotubulesintheneonatalrathippocampusandpotentiallyresultingindamagetohippocampalneurons.

简介：摘要目的探索脑脊液标志物，尤其是总tau蛋白（T-tau）及磷酸化tau蛋白（P-tau）对Creutzfeldt-Jakob病（Creutzfeldt-Jakob disease，CJD）的诊断与鉴别诊断价值。方法按2009年Brain标准及2018年Neurology改良版标准选取2018—2019年北京协和医院脑脊液生物标志物研究队列中的散发性CJD（sporadic CJD，sCJD）患者。按2011年美国国立老化研究所与阿尔茨海默病（AD）协会标准选择年龄、性别相对匹配的AD患者以及认知功能正常的其他神经系统疾病患者作为对照病例，应用其脑脊液标本进行分组对照研究。共收集了12例sCJD患者入组，同时收集49例AD患者以及14名认知正常者入对照组。所有脑脊液标本均为腰椎穿刺时直接滴落收集，-80 ℃保存，由专门实验室及指定实验员进行T-tau蛋白、P-tau蛋白测定。同时收集sCJD患者影像学及脑电图资料，并按规定将sCJD病例报送中国疾病预防控制中心，检测14-3-3蛋白及相关的基因。结果通过非参数秩和检验对比3组人群脑脊液tau蛋白含量，结果显示sCJD组T-tau水平达1 211（448，2 227）pg/ml，AD组T-tau水平达549（314，1 078）pg/ml，均显著高于对照组[127（79，192）pg/ml，U=20、73，P<0.01]。sCJD组的T-tau蛋白水平升高更明显，显著高于AD患者（U=178，P=0.034 9）。在AD患者中，P-tau水平达72（58，109）pg/ml，较对照组[27（15，42）pg/ml]显著升高（U=82，P<0.01），但在sCJD患者[32（24，47）pg/ml]无明显升高。sCJD患者的T-tau/P-tau比值[29.77（20.01，54.53）]高于AD[7.45（4.79，10.43）；U=87，P<0.01）。12例sCJD头颅MRI均存在"花边征"，5例存在脑电图三相波改变。9例sCJD患者被上报至中国疾病防治中心，其中4例14-3-3蛋白阳性；9例朊蛋白PRNP基因均无突变，129位密码子均为M/M型，219位密码子均为E/E型。结论sCJD患者脑脊液tau蛋白、T-tau/P-tau显著增高，对于sCJD的诊断及鉴别具有一定价值。

简介：ThepresentstudywasdesignedtodeterminethechangesofphosphorylationofcAMP-responseele-mentbindingprotein(CREB)inhippocampusinducedbyohmefentanylstereoisomers(F9202andF9204)inconditionedplacepreference(CPP)paradigm.TheresultsshowedthatmicereceivingF9202andF9204displayedobviousCPP.TheycouldallsignificantlystimulateCREBphosphorylationandmaintainedforalongtimewithoutaffectingtotalCREBproteinlevels.TheeffectofF9204wassimilartomorphinewhicheffectwasmorepotentandlongerthanF9202.Wealsoexaminedtheeffectsofketamine,anoncompetitiveN-mthyl-D-aspartatereceptor(NR)antagonist,onmorphine-,F9202-andF9204-inducedCPPandphos-phorylationofCREBinhippocampus.KetaminecouldsuppressnotonlytheplacepreferencebutalsothephosphorylationofCREBproducedbymorphine,F9202andF9204.ThesefindingssuggestthatalterationsinthephosphorylationofCREBberelevanttoopiatessignalingandthedevelopmentofopiatesdependence.NRantagonistsmayinterferewithopiatesdependenceandmayhavepotentialtherapeuticimplications.

简介：摘要目的观察脊髓缺血再灌注损伤（SCII）后神经元Tau蛋白与磷酸化-Tau（p-Tau）蛋白表达的变化。方法取健康成年SD大鼠96只，随机分为假手术（仅建模不制造损伤）组（n=48）及SCII（制造SCII模型）组（n=48）。建模后均于3、6、12、24、48、72 h（n=8）取L4~L5节段脊髓进行免疫组织化学染色以观察脊髓神经元凋亡情况，并比较假手术组与SCII组间及同一个组内各个时间点Tau蛋白、p-Tau蛋白的表达。结果假手术组细胞完整，灰质部分细胞密集，少数细胞内可见Tau蛋白表达，细胞核周及细胞质少量丝状p-Tau蛋白表达，Tau蛋白和p-Tau蛋白表达量在各个时间点间比较差异均无统计学意义（P>0.05）。SCII组凋亡细胞间可见散在的Tau蛋白阳性表达，未凋亡细胞内可见明显的强阳性表达；Tau蛋白表达量在损伤后逐渐增加，48 h达到峰值，72 h趋于平稳；除72 h外，各时间点间两两比较差异均有统计学意义（P<0.05）。SCII组在各凋亡细胞细胞质间可见条索状及片状p-Tau蛋白阳性表达；p-Tau蛋白表达量在6 h内迅速增高，6 h后未见明显变化，其后各时间点间两两比较差异均无统计学意义（P>0.05）。各时间点SCII组的Tau蛋白和p-Tau蛋白表达量组均高于假手术组，差异有统计学意义（P<0.05）。结论SCII后6~48 h内调控Tau蛋白和p-Tau蛋白的表达有望减轻脊髓损伤的严重程度。

简介：摘要Tau蛋白的异常累积是阿尔茨海默病（AD）及非AD类Tau蛋白病的主要病理学特征，并且与神经变性和认知障碍密切相关。近年来，第一代特异性Tau蛋白PET分子探针已经被研发，并进行了临床试验。因第一代PET分子探针中常出现脱靶结合，促进了具有更高结合力和选择性的第二代特异性Tau蛋白PET分子探针的研发。笔者综述了Tau蛋白PET显像作为AD病理学生物标志物的潜力和Tau蛋白分子探针的最新进展。

简介：Tau蛋白是一种微管相关性蛋白,在中枢神经轴突运输中起着重要作用,在神经变性疾病中扮演着重要角色.以Tau蛋白为病理基础、以运动异常为主要表现或兼有运动异常及痴呆表现的综合征被称为"Tau蛋白病理相关性运动异常",主要包括与17号染色体相关的额颞叶痴呆和帕金森综合征(frontotemporaldementiawithparkinsonismlinkedtochromosome17,FTDP-17),进行性核上性麻痹(progressivesupranuclearpalsy,PSP),以及皮质基底节变性(cortico-basaldegeneration,CBD)等,其中FTDP-17为以Tau蛋白为病理基础的家族性疾病的代表,而后两者则为散发性疾病的代表.现仅将在临床表现、分子遗传学改变和病理基础等方面对这类疾病的研究进展综述如下.

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简介：Therearecurrentlynofederallyapprovedneuroprotectiveagentstotreattraumaticbraininjury.Progesterone,ahydrophobicsteroidhormone,hasbeenshowninrecentstudiestoexhibitneuroprotectiveeffectsincontrolledcorticalimpactratmodels.Aktisaproteinkinaseknowntoplayaroleincellsignalingpathwaysthatreduceedema,inflammation,apoptosis,andpromotecellgrowthinthebrain.ThisstudyaimstodetermineifprogesteronemodulatesthephosphorylationofAktviaitsthreonine308phosphorylationsite.Phosphorylationatthethreonine308siteisoneofseveralsitesresponsibleforactivatingAktandenablingtheproteinkinasetocarryoutitsneuroprotectiveeffects.ToassesstheeffectsofprogesteroneonAktphosphorylation,C57BL/6miceweretreatedwithprogesterone(8mg/kg)at1(intraperitonally),6,24,and48hours(subcutaneously)postclosed-skulltraumaticbraininjury.Thehippocampuswasharvestedat72hourspostinjuryandpreparedforwesternblotanalysis.TraumaticbraininjurycausedasignificantdecreaseinAktphosphorylationcomparedtoshamoperation.However,micetreatedwithprogesteronefollowingtraumaticbraininjuryhadanincreaseinphosphorylationofAktcomparedtotraumaticbraininjuryvehicle.Ourfindingssuggestthatprogesteroneisaviabletreatmentoptionforactivatingneuroprotectivepathwaysaftertraumaticbraininjury.

简介：AbstractBackground:According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient’s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

简介：Aim:TostudytheeffectofEcdysterone(ECR)ontheexpressionofTaufromthecerebralcorticeandhippocampusandbehaviorsinpassiveavoidancereactionandspatialdiscriminationofthemiceinducedbyoverloadaluminumsalt.MethodsFourty-fiveNIHmicewererandomlydividedintofivegroups,thecontrolgroup,themodelgroup,thetreated

简介：摘要“原发性年龄相关tau蛋白病”（PART）是见于高龄老人的神经系统退行性疾病，临床表现类似阿尔茨海默病，确诊有赖于病理证实脑内有神经原纤维缠结而缺乏或仅有少量淀粉样斑。文中对PART的历史沿革、临床表现、病理特点及诊断等进行综述，以期为临床诊治提供新思路。

简介：摘要目的观察益智灵胶囊对Aβ1-42致阿尔茨海默病模型大鼠Tau蛋白、磷酸化Tau蛋白及Aβ1-42表达影响，并对其可能的机制进行初步探讨。方法通过在大鼠海马区立体定向注射凝聚态Aβ1-42复制AD动物模型,采用免疫组织化学法检测大鼠脑神经细胞T-Tau蛋白和P-Tau蛋白的表达情况及大鼠大脑Aβ1-42表达的变化。将SD大鼠随机分为7组。假手术组右侧海马单次注射生理盐水5μL，模型组、石杉碱甲组及益智灵各组分别右侧海马注射Aβ1-42(10μg),阳性药组和益智灵各组分别灌胃给予石杉碱和益智灵提取物。给药3周后，采用免疫组织化学法检测海马区Aβ、Tau蛋白、磷酸化Ta蛋白表达。结果益智灵可通过抑制Aβ1-42聚集、降低T-tau及P-tau浓度，从而起到早期干预AD的作用。结论益智灵提取物能改善Aβ1-42引起阿尔茨海默病大鼠学习记忆障碍，其机制可能与抑制Aβ1-42聚集、降低T-tau及P-tau浓度有关。

简介：在神经变性疾病患者的脑内神经元内包含体中，神经原纤维缠结（NFTs）是最常见的，它可能介导了神经元的死亡和认知障碍。本研究作者发现表达可抑制的人tau变异型的小鼠产生了进行性年龄相关的神经原纤维缠结（NFTs）、神经元丧失以及行为缺陷。抑制转基因tau后，记忆功能恢复，神经元数目稳定。但令人吃惊的是，这时神经原纤维缠结（NFTs）依然累积。这样来看，神经原纤维缠结（NFTs）不足于导致此种病理模型的认知衰减或神经元死亡。