Genetics and Molecular Biology Parkinsonism

遗传学和分子生物学帕金森病

• 批准号: 8337451
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 62万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8337451
• 关键词: Achievement; Administrator; Advisory Committees; Aging; Alzheimer' s Disease; American; Animal Model; Animals; Area; Autopsy; Award; Biochemical; Biological Assay; Biological Markers; Biological Models; Book Chapters; Boston; Brain; Case Study; Cell Culture Techniques; Cell Line; Cell model; Cells; China; Chromosomes, Human, Pair 17; Clinic; Clinical; Clinical Data; Cognition Disorders; Collaborations; Collection; Common Data Element; Communities; Complement; Complication; Consensus; County; Custom; Cytopathology; DNA; Data; Data Element; Data Set; Databases; Dementia; Development; Diagnostic; Disease; Disease Association; Doctor of Philosophy; Drug Delivery Systems; Drug Formulations; Dystonia; Education and Outreach; Educational Activities; Enrollment; Eukaryotic Initiation Factor-4G; Europe; Evaluation; Exclusion Criteria; FTD with parkinsonism; Faculty; Family; Fellowship; Foundations; Foxes; Frontotemporal Dementia; Funding; Genes; Genetic; Genetic Materials; Genetic Screening; Genetic screening method; Goals; Grant; Histologic; Human; Hypercapnic respiratory failure; Impaired cognition; Incidental Discoveries; Institutes; Interdisciplinary Study; International; Internet; Israel; Japan; Knowledge; LRRK2 gene; Laboratories; Lead; Leadership; Lewy Bodies; Lewy Body Disease; Link; Longitudinal Studies; MPTP Poisoning; Medical Education; Medical Research; Mental Depression; Mentors; Methods; Minnesota; Mission; Modeling; Molecular; Molecular Biology; Molecular Genetics; Motor; Movement Disorders; Multiple System Atrophy; Mutation; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Neurologic; Neurologist; Northern Africa; Onset of illness; Operon; Outcome; Paper; Parkinson Disease; Parkinson' s Dementia; Parkinsonian Disorders; Pathogenesis; Pathologic; Patient Education; Patient Recruitments; Patients; Peer Review; Pennsylvania; Pharmacologic Substance; Phosphotransferases; Play; Postdoctoral Fellow; Preclinical Drug Evaluation; Predisposition; Process; Productivity; Progressive Supranuclear Palsy; Prospective Studies; Protein Binding Domain; Proteomics; Publications; RNA Interference; Recruitment Activity; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Resource Sharing; Resources; Restless Legs Syndrome; Risk; Risk Factors; SNCA gene; Saimiri; Sampling; Scandinavia; Scheme; Scientist; Series; South America; Staging; Subgroup; Sum; Support Groups; Syndrome; System; Taiwan; Targeted Research; Tetanus Helper Peptide; Therapeutic; Therapeutic Uses; Time; Toxic effect; Training; Translating; Translational Research; Travel; Universities; Variant; Veins; Washington; Woman; Work; advanced disease; alpha synuclein; arm; base; brain tissue; candidate identification; clinical material; corticobasal degeneration; cytotoxicity; disability; dynactin; early onset; follow-up; gene discovery; genetic linkage; genetic risk factor; genetic variant; genome wide association study; genome-wide; illness length; inclusion criteria; inhibitor/antagonist; insight; interest; kindred; leucine-rich repeat kinase 2; meetings; member; molecular pathology; neuroblastoma cell; neuropathology; next generation; novel; outreach; population based; posters; pre-clinical; pre-doctoral; prevent; programs; prospective; skills; small molecule; small molecule libraries; success; therapeutic target; viral gene delivery; web page

The Udall Center for Excellence in Parkinson Disease Research at the Mayo Clinic is an integrated, multidisciplinary research program of neurologists, neuropsychologists, geneticists, neuropathologists and basic scientists in the study of the "Genetics and Molecular Biology of Parkinsonism." The Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section and longitudinal studies of Parkinson disease (PD) and dementia with Lewy bodies (DLB) for the clinical material used in the research projects, as well as strong institutional commitment to PD research. The research proposed is highly synergistic despite the wide range of expertise and scientific background of the members of the Udall team. Each member of the team brings unique knowledge and skill sets to the mission, and together we are greater than the sum of the parts. The work proposed builds upon highly successful and productive cores that have been working together for over a decade. The clinical, genetic and pathologic resources are rivaled by few centers. The Mayo Udall Center is a unique complement to the Udall Center program. Success of our Udall Center has been based upon building successful collaborations and generous sharing of resources and data. This proposal has the overarching goal to better understand Lewy-related PD, which is the most common form of PD. Lewy bodies are also the hallmark of DLB and PD with dementia (PDD). How PDD and DLB relate to each other is unknown, but this non-motor complication of PD is of increasing interest to the Parkinson community. Strengths of our Udall Center are the large collection of multi-incident PD families, a proven track record of success in discovery of PD genes and a large collection of PD, PDD and DLB brains in a well annotated brain bank. The research proposal has three projects and five cores: Project 1. "Identification of genetic risk factors that predict disease onset, susceptibility and progression of PD," (PL: Matthew J. Farrer, PhD); Project 2. "Identification of candidate therapeutics for a-synuclein aggregation and cytotoxicity," (PL: Shu-Hui C. Yen, PhD); Project 3. "Molecular pathology of Lewy-related cognitive dysfunction," (PL: Dennis W. Dickson, MD); Core A. Administrative (CL: Dennis W. Dickson, MD); Core B. Clinical (CL: Zbigniew K. Wszolek, MD); Core C. Genetic (CL: Matthew J. Farrer PhD); Core D. Neuropathology (CL: Dennis W. Dickson MD) and Core E. Education and Outreach (CL: Ryan J. Uitti, MD).

马约诊所的Udall帕金森病研究卓越中心是一个综合性的多学科研究项目，由神经学家、神经心理学家、遗传学家、神经病理学家和基础科学家组成，研究“帕金森病的遗传学和分子生物学”。“该中心利用马约诊所运动障碍科的临床优势和帕金森病（PD）和路易体痴呆（DLB）的纵向研究，为研究项目中使用的临床材料，以及对PD研究的坚定机构承诺。尽管Udall团队成员拥有广泛的专业知识和科学背景，但拟议的研究具有高度的协同作用。团队的每个成员都为使命带来了独特的知识和技能，我们在一起比部分的总和更大。拟议的工作建立在十多年来一直合作的非常成功和富有成效的核心之上。临床、遗传和病理学资源很少有中心能与之匹敌。马约尤德尔中心是尤德尔中心计划的独特补充。我们的Udall中心的成功是基于建立成功的合作和慷慨的资源和数据共享。 该提案的首要目标是更好地了解路易相关PD，这是PD的最常见形式。路易体也是DLB和PD伴痴呆（PDD）的标志。PDD和DLB如何相互关联尚不清楚，但PD的这种非运动并发症越来越受到帕金森社区的关注。我们的Udall中心的优势是大量收集多事件PD家族，成功发现PD基因的可靠记录，以及在注释良好的脑库中大量收集PD，PDD和DLB大脑。研究方案有三个项目和五个核心：项目1。“预测疾病发作、易感性和PD进展的遗传风险因素的识别”（PL：Matthew J. Farrer，PhD）;项目2。“用于α-突触核蛋白聚集和细胞毒性的候选治疗剂的鉴定”（PL：Shu-Hui C. Yen，PhD）; Project 3.“路易相关认知功能障碍的分子病理学”（PL：Dennis W。Dickson，MD）; Core A.行政（CL：Dennis W. Dickson，MD）;核心B。临床（CL：Zbigniew K. Wszolek，MD）; Core C.遗传学（CL：Matthew J. Farrer PhD）;核心D。神经病理学（CL：Dennis W. Dickson MD）和Core E.教育和推广（CL：瑞安J. Uitti，医学博士）。