Genetics and Molecular Biology of Parkinsonism

帕金森病的遗传学和分子生物学

• 批准号: 7497315
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 10万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497315
• 关键词: Adrenergic Agents; Affect; Age; Aging; All Sites; Alzheimer' s Disease; Amish; Animal Model; Animals; Archives; Arizona; Authorization documentation; Autopsy; Basic Science; Belgium; Biochemical; Biological Markers; Blood; Botox; Botulinum Toxin Type A; Botulinum Toxins; Brain; CEP 1347; Calcinosis; Canada; Carbidopa; Cardiac; Caring; Case Study; Cell Death; Cell Line; Cerebrum; Cervical Dystonia; Chromosomes, Human, Pair 17; Classification; Clinic; Clinical; Clinical Paths; Clinical Research; Clinical Trials; Collaborations; Communication; Complement; Computers; Condition; Controlled Study; Correlative Study; Creatine; DNA; Daily; Data; Dementia; Detection; Diagnosis; Digit structure; Disease; Dose; Double-Blind Method; Drug Industry; Dystonia; Elan brand of botulinum toxin type B; Electrophysiology (science); Environment; Epidemiology; Essential Tremor; Estrogens; Europe; Evaluation; Event; Faculty; Family; Family Sizes; Florida; France; Frequencies; Funding; Futility; Future; Gene Expression; Genes; Genetic; Genetic Screening; Genets; Genotype; Germany; Goals; Grant; Hand functions; Hemifacial Spasm; Histologic; Human; Human Resources; Individual; Inflammation; Inpatients; Investigation; Investments; Italy; Japan; KW-6002; Label; Laboratories; Lead; Levodopa; Lewy Bodies; Lewy Body Disease; Light; Longitudinal Studies; MSMB gene; Mails; Maps; Measures; Medical Record Linkage; Menopause; Minnesota; Minocycline; Mitochondria; Modeling; Molecular Biology; Molecular Epidemiology; Molecular Genetics; Motion; Motor; Movement; Movement Disorders; Multicenter Studies; Mutation; Names; Nerve Degeneration; Neurology; Neuropsychology; Norway; Numbers; Operative Surgical Procedures; Other Therapy; Oxidative Stress; Parkinson Disease; Parkinson' s Dementia; Parkinsonian Disorders; Pathologic; Pathology; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Placebo Control; Play; Poland; Population; Population Genetics; Population Heterogeneity; Principal Investigator; Process; Progressive Supranuclear Palsy; Proteins; Proteomics; Quality of Care; Randomized; Range; Recruitment Activity; Reporting; Research; Research Ethics Committees; Research Personnel; Research Project Grants; Resources; Restless Legs Syndrome; Risk; Role; Rome; Rotenone; Running; Safety; Sampling; Scheme; Services; Site; Societies; Speech; Staging; Surveys; Syndrome; System; TPO gene; Tablets; Tauopathies; Telecommunications; Testing; Time; Toxin; Transgenic Mice; Transgenic Organisms; Transglutaminases; Travel; Treatment Protocols; Tremor; United States; United States National Institutes of Health; Universities; Videoconferences; Videoconferencing; Washington; Week; Women' s Health; Wrist; adrenergic; alpha synuclein; base; behavior test; botulinum toxin type B; brain tissue; calcification; cohort; day; disease phenotype; early onset; follow-up; genetic epidemiology; genome-wide linkage; improved; in vitro Assay; interest; kindred; member; multicatalytic endopeptidase complex; multidisciplinary; mutant; nerve supply; neuron loss; neuropathology; news; parkin gene/protein; patient registry; pre-clinical; professor; programs; repository; research study; response; ropinirole; size; synuclein; tau Proteins; tau expression; transmission process; valproate

The Udall Center for Excellence in Parkinson's Disease Research at the Mayo Clinic is an integrated, multidisciplinary center that studies the Genetics and Molecular Biology of Parkinsonism. The Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section as well as epidemiologic and longitudinal studies of Parkinson's disease (PD), dementia with Lewy bodies and aging that provide clinical material for research projects. The Clinical Core is a multi-national effort to identify and characterize multiplex families with PD for genetic studies of PD. The Clinical Core also recruits and follows sporadic PD patients and arranges for postmortem studies. The Genetic Core provides genetic screening and performs genome wide linkage studies of familial PD. When permission is granted, samples are submitted to the NINDS DNA repository. The Genetic Core serves Project 4 by assessing transgenic integration site, copy number and strain background. The Neuropathology Core performs postmortem evaluations of PD, provides histologic support for projects and provides postmortem material collected through several different avenues for the research projects. Project 1 builds upon progress from the previous funding period demonstrating multiplication of the a-synuclein gene (SCNA) in autosomal dominant, early-onset PD and focuses on population genetics of SNCA, characterization of SNCA multiplications (including the size and genes within the multiplication regions), and measuring temporal and regional _-synuclein expression in normals and a-synucleinopathies. Project 2 is a clinicopathologic study that determines the frequency and clinical expression of Lewy bodies in normal individuals using the Mayo Medical Records Linkage System, with studies on the role of neuronal loss, inflammation and tau on clinical feaures. Project 3 uses cell lines that inducibly express a-synuclein as well as mitochondrial toxins, such as rotenone, to study truncated and aggregated a-synuclein with the goal of determining the role of interacting proteins in aggregate formation and the effects of aggregates on proteasome function and gene expression. Project 4 is a multidisciplinary study of transgenic mice with conditional expression of a-synuclein that tests the hypothesis that synucleinopathy can be reversed and that aging, oxidative stress and transglutaminase contribute to the synucleinopathy.

马约诊所的尤德尔帕金森病研究卓越中心是一个综合性的， 多学科中心，研究遗传学和分子生物学帕金森症。中心 借鉴了马约诊所运动障碍科的临床优势以及流行病学 帕金森病（PD）、路易体痴呆和衰老的纵向研究， 研究项目的临床材料。临床核心是一个多国努力，以确定和 描述PD多重家系的特征，用于PD的遗传学研究。临床核心还招募和 跟踪散发性PD患者并安排尸检研究。基因核心提供基因 筛选并进行家族性PD的全基因组连锁研究。当获得许可后， 样本被提交到NINDS DNA储存库。基因核心服务于项目4， 转基因整合位点、拷贝数和菌株背景。神经病理学核心执行 PD的尸检评估，为项目提供组织学支持，并提供尸检材料 通过几个不同的渠道收集的研究项目。项目1以进展为基础 来自上一个资助期的研究，证明了a-突触核蛋白基因（SCNA）在 常染色体显性遗传，早发性PD，重点是SNCA的群体遗传学， SNCA扩增（包括扩增区域内的大小和基因），并测量 正常人和α-突触核蛋白病中时间和区域α-突触核蛋白表达。项目2是一个 一项临床病理学研究，确定正常人中路易体的频率和临床表达。 使用马约医疗记录链接系统的个人，对神经元损失的作用进行研究， 炎症和tau蛋白对临床特征的影响。项目3使用可诱导表达α-突触核蛋白的细胞系， 以及线粒体毒素，如鱼藤酮，以研究截短和聚集的α-突触核蛋白， 目的是确定相互作用蛋白质在聚集体形成中的作用和聚集体的影响 对蛋白酶体功能和基因表达的影响。项目4是一项关于转基因小鼠的多学科研究 用条件性表达α-突触核蛋白来检验突触核蛋白病可以逆转的假设 以及衰老、氧化应激和转氨酶导致突触核蛋白病。