Genetics and Molecular Biology of Parkinsonism

帕金森病的遗传学和分子生物学

• 批准号: 8432571
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 145.93万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8432571
• 关键词: Genetics; Molecular; Biology; Parkinsonism

DESCRIPTION (provided by applicant): The Udall Center for Excellence in Parkinson Disease Research at the Mayo Clinic is an integrated, multi-disciplinary research program focusing on of the "Genetics and Molecular Biology of Parkinsonism." The Udall Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section with its longitudinal studies of Parkinson disease (PD) and a focus on the clinical genetics of familial Parkinsonism, a large brain bank of Parkinsonian disorders and strong institutional commitment to PD research and education. All components of the Udall Center are based in Jacksonville, Florida, although core resources in Rochester, Minnesota, particularly the Division of Biomedical Statistics will be used. Mayo Foundation educational resources, including sponsored seminar series and graduate level educational courses on PD and other neurodegenerative disorders are also utilized. The proposal is highly innovative and original in that it addresses the intriguing interaction between two molecules with surprising similarities, tau and a-synuclein, both of which are strongly implicated as critical factors in pathogenesis of parkinsonian disorders. The clinical, genetic and pathologic studies proposed capitalize on inherent strengths of the Udall Center investigators and unique clinical, genetic and pathological resources that have been built over the years due to the fervent devotion of investigators to better understanding PD and related disorders. The Center also brings established investigators in complementary areas of research (Drs. Rademakers and Petrucelli) to the task of understanding how tau is related PD and how tau-directed therapies may translate into novel treatments for PD and parkinsonian tauopathies. The proposed Center will have three projects and four cores with an overarching theme to understand the role of tau in PD and parkinsonian tauopathies. Project 1, entitled "Identification of novel parkinsonian genes by whole-genome sequencing," is led by Rosa Rademakers, PhD. Project 2, entitled "Genetic determinants of a-synuclein and tau pathology in Parkinsonism," is led by Dennis W. Dickson, MD. Project 3, entitled "Identification and testing of novel compounds to treat Parkinsonism," is led by Leonard Petrucelli, PhD. Core A (Administration) and Core D (Neuropathology) are led by Dennis W. Dickson, MD. Core B (Clinical) is led by Zbigniew K. Wszoiek, MD. Core C (Genetics) is led by Owen A. Ross, PhD. PUBLIC HEALTH RELEVANCE: Parkinson disease (PD) is one of the leading causes of neurologic disability. Increasingly, it is recognized that there is a genetic component to risk for PD and related disorders sometimes referred to as Parkinsonism-plus. Research in our Center will find new genes for familial PD and increase our understanding of how common differences in the genetic make-up of individuals leads to sporadic PD. Finally, our research will work towards discovering drugs that can treat PD and Parkinsonism-plus disorders.

描述（由申请人提供）：马约诊所的Udall帕金森病研究卓越中心是一个综合的、多学科的研究项目，专注于“帕金森病的遗传学和分子生物学”。“Udall中心借鉴了马约诊所运动障碍科的临床优势，其对帕金森病（PD）的纵向研究，并专注于家族性帕金森病的临床遗传学，帕金森病的大型脑库和对PD研究和教育的强大机构承诺。Udall中心的所有组成部分都设在佛罗里达的杰克逊维尔，但将使用明尼苏达州罗切斯特的核心资源，特别是生物医学统计司。还利用了马约基金会的教育资源，包括关于PD和其他神经退行性疾病的赞助研讨会系列和研究生水平的教育课程。该提议是高度创新和原创的，因为它解决了具有惊人相似性的两种分子tau和α-突触核蛋白之间有趣的相互作用，这两种分子都强烈暗示为帕金森病发病机制中的关键因素。临床，遗传和病理学研究建议利用Udall中心研究人员的固有优势和独特的临床，遗传和病理学资源，这些资源是多年来由于研究人员的热情投入而建立的，以更好地了解PD和相关疾病。该中心还将补充研究领域的研究人员（Rademakers和Petrucelli博士）带到了解tau如何与PD相关以及tau导向疗法如何转化为PD和帕金森病tau蛋白病的新疗法的任务中。拟议的中心将有三个项目和四个核心，其总体主题是了解tau在PD和帕金森病中的作用。项目1名为“通过全基因组测序鉴定新的帕金森病基因”，由Rosa Rademakers博士领导。项目2，题为“遗传决定因素的α-突触核蛋白和tau病理帕金森症，”是由丹尼斯W。Dickson，MD.项目3名为“治疗帕金森病的新型化合物的鉴定和测试”，由伦纳德彼得鲁塞利博士领导。核心A（管理）和核心D（神经病理学）由Dennis W. Dickson，MD.核心B（临床）由Zbigniew K. Wszoiek，MD. Core C（Genetics）由Owen A领导。Ross博士 公共卫生相关性：帕金森病（PD）是神经功能障碍的主要原因之一。越来越多的人认识到，有一个遗传因素的风险， PD和相关疾病有时被称为Parkinsonism-plus。我们中心的研究将发现家族性PD的新基因，并增加我们对个体遗传组成中常见差异如何导致散发性PD的理解。最后，我们的研究将致力于发现可以治疗PD和帕金森病的药物。