The role of Mnbk in Downs Syndrome brain development and aging
Mnbk 在唐氏综合症大脑发育和衰老中的作用
基本信息
- 批准号:7392658
- 负责人:
- 金额:$ 52.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-01-01 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgeAge-YearsAgingAlzheimer&aposs DiseaseAmygdaloid structureAmyloidosisAtaxiaAxonBiochemicalBody of uterusBrainCell AgingCerebellumCharacteristicsChildChromosome MappingChromosomes, Human, Pair 21Clinical ResearchCognitiveComplexCongenital Heart DefectsCorpora amylaceaCorpus striatum structureDataDefectDementiaDepositionDeteriorationDevelopmentDiagnosisDiseaseDown SyndromeDrosophila genusDynaminDynamin IEndocrine systemEpilepsyExhibitsFoundationsGenesGlobus PallidusGoalsHeadHippocampal FormationHippocampus (Brain)ImmuneIn VitroIndividualJudgmentLevodopaLewy BodiesLifeLimb structureLinkLocalizedLongevityLow PrevalenceManuscriptsMemoryMental RetardationMitochondriaModelingModificationMolecular BiologyMotorMotor ActivityMotor CortexMotor SkillsMovementMusMuscle hypotoniaNerve DegenerationNeuritesNeuronsNucleus AccumbensNumbersParkinson DiseaseParkinsonian DisordersPathologyPatternPedunculopontine Tegmental NucleusPhosphorylationPhosphotransferasesPilot ProjectsPlayPreparationPresenile Alzheimer DementiaPresynaptic TerminalsProtein OverexpressionProteinsRangeRateReactionRecyclingRest TremorRiskRisk FactorsRoleShapesShuffling GaitsSpecificityStagingStressStructureSubstantia nigra structureSynapsesSynaptic VesiclesSystemThalamic structureYakage relatedagedaging brainamphiphysinbasebrain sizecaudate nucleuscell agedevelopmental diseaseearly onsetentorhinal cortexfunctional disabilityfunctional lossimprovedmorphometryneurogenesisneuron lossneuropathologynormal agingputamenresearch studyresponseself helpsensorimotor systemsocialsynaptic functionvirtualyoung adult
项目摘要
DESCRIPTION (provided by applicant): We propose to integrate molecular biology, morphometry, and clinical studies to identify mechanisms leading to abnormal brain development, accelerated aging, and early onset of Alzheimer disease in people with Down syndrome (DS). We plan to conduct biochemical and morphometric studies of the memory system (hippocampus, amygdala, and entorhinal cortex) and sensory-motor system ( substantia nigra, pedunculopontine tegmental nucleus, caudal intralaminar thalamus, caudate nucleus, putamen, globus pallidus, nucleus accumbens, motor cortex, and cerebellum) in 44 people with DS. Because all people with DS develop early onset AD and some develop parkinsonian-type neurodegeneration, the mechanisms of neuronal loss in DS will be compared with temporal and topographic patterns of neuronal degeneration and loss in sporadic AD (30 cases), idiopathic PD (30 cases), and normal aging (44 cases). Our goal will be to determine: (1) the role of abnormal expression of Mnbk/DyrklA in developmental neuronal deficits in the memory and motor system of people with DS; (2) the mechanisms of synaptic abnormalities caused by excess of Mnbk/Dyrk1A protein in people with DS; (3) the role of Mnbk/Dyrk1A protein in brain accelerated aging during the fourth decade of life in people with DS; (4) the contribution of different mechanisms of neurodegeneration to dementia and motor deterioration in people with DS over 40 years of age; (5) modifications in the contribution of neurodegenerative changes to neuronal and functional loss in people with DS in comparison to normal aging, sporadic AD, and idiopathic PD. We hypothesize that in DS the extra copy of the Mnbk/Dyrk1A gene is not only a key factor in shaping structural and functional developmental abnormalities, but also affects the function of synapses in adulthood, contributes to accelerating aging of the brain, and changes the structural and functional background for development of AD and PD pathology. We hypothesize that we will be able to identify DS-specific modifications of the course of AD and PD pathology. This study will provide a foundation for identifying the mechanisms and morphological substrate of specific functional deficits, and should contribute to the improvement of diagnosis and treatment.
描述(由申请人提供):我们建议整合分子生物学、形态计量学和临床研究,以确定导致唐氏综合症(DS)患者大脑发育异常、衰老加速和阿尔茨海默病早期发病的机制。我们计划对44例DS患者的记忆系统(海马体、杏仁核和内嗅觉皮质)和感觉-运动系统(黑质、桥脑被盖核、丘脑尾侧内层、尾状核、壳核、苍白球、伏隔核、运动皮质和小脑)进行生化和形态计量学研究。由于DS患者全部发展为早发性AD,部分患者发展为帕金森型神经退行性变,因此DS的神经元丢失机制将与散发性AD(30例)、特发性PD(30例)和正常衰老(44例)的神经元变性和丢失的时间和地形图模式进行比较。我们的目标将是确定:(1)Mnbk/DyrkA异常表达在DS患者记忆和运动系统发育神经元缺陷中的作用;(2)DS患者由于Mnbk/Dyrk1A蛋白过多而导致突触异常的机制;(3)在DS患者生命的第四个十年中,Mnbk/Dyrk1A蛋白在脑加速衰老中的作用;(4)不同的神经退变机制在40岁以上DS患者痴呆和运动恶化中的作用;(5)与正常衰老、散发性阿尔茨海默病和特发性帕金森病相比,DS患者神经退行性改变对神经元和功能丧失的贡献的改变。我们推测,在DS中,Mnbk/Dyrk1A基因的额外拷贝不仅是形成结构和功能发育异常的关键因素,而且还影响成年后突触的功能,有助于加速脑老化,并改变AD和PD病理发生的结构和功能背景。我们假设我们将能够识别AD和PD病理过程中DS特异性的修饰。这项研究将为明确特定功能缺陷的机制和形态基础提供基础,并将有助于提高诊断和治疗水平。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome.
- DOI:10.3233/jad-2008-13307
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:Zhihou Liang;Fei Liu;K. Iqbal;I. Grundke‐Iqbal;J. Wegiel;C. Gong
- 通讯作者:Zhihou Liang;Fei Liu;K. Iqbal;I. Grundke‐Iqbal;J. Wegiel;C. Gong
Activity-dependent phosphorylation of dynamin 1 at serine 857.
动力蛋白 1 在丝氨酸 857 处的活性依赖性磷酸化。
- DOI:10.1021/bi2017798
- 发表时间:2012
- 期刊:
- 影响因子:2.9
- 作者:Xie,Wen;Adayev,Tatyana;Zhu,Huiyuan;Wegiel,Jerzy;Wieraszko,Andrzej;Hwang,Yu-Wen
- 通讯作者:Hwang,Yu-Wen
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JERZY WEGIEL其他文献
JERZY WEGIEL的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JERZY WEGIEL', 18)}}的其他基金
The role of Mnbk in DS brain development and aging
Mnbk 在 DS 大脑发育和衰老中的作用
- 批准号:
6835706 - 财政年份:2004
- 资助金额:
$ 52.18万 - 项目类别:
The role of Mnbk in DS brain development and aging
Mnbk 在 DS 大脑发育和衰老中的作用
- 批准号:
7002635 - 财政年份:2004
- 资助金额:
$ 52.18万 - 项目类别:
Role of Mnbk in Downs Syndrome brain development & aging
Mnbk 在唐氏综合症大脑发育中的作用
- 批准号:
6723287 - 财政年份:2004
- 资助金额:
$ 52.18万 - 项目类别:
The role of Mnbk in Downs Syndrome brain development and aging
Mnbk 在唐氏综合症大脑发育和衰老中的作用
- 批准号:
7156226 - 财政年份:2004
- 资助金额:
$ 52.18万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 52.18万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 52.18万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 52.18万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 52.18万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 52.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 52.18万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 52.18万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 52.18万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 52.18万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 52.18万 - 项目类别:
Miscellaneous Programs