Genetics and Molecular Biology of Parkinsonism

描述(由申请人提供)：梅奥诊所的尤德尔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研究。尤德尔中心利用梅奥临床运动障碍科的临床优势，对帕金森病(PD)进行纵向研究，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，以及对PD研究和教育的坚定机构承诺。Udall中心的所有组成部分都设在佛罗里达州杰克逊维尔，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。还利用了梅奥基金会的教育资源，包括关于帕金森病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。该提案具有很高的创新性和原创性，因为它解决了两个分子之间有趣的相互作用，这两个分子具有惊人的相似性，tau和a-突触核蛋白，这两个分子都是帕金森病发病的关键因素。拟议的临床、遗传和病理研究充分利用了尤德尔中心研究人员的内在优势以及多年来建立的独特的临床、遗传和病理资源，这是由于研究人员热衷于更好地了解帕金森病和相关疾病。该中心还邀请互补研究领域的资深研究人员(Rademaker博士和Petrucelli博士)参与了解tau与帕金森病相关的任务，以及tau导向疗法如何转化为帕金森病和帕金森病的新疗法。拟议的中心将有三个项目和四个核心，以了解tau在帕金森氏症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”，由罗莎·拉德梅克斯博士领导。项目2由医学博士丹尼斯·W·迪克森领导，题为“帕金森病中α-突触核蛋白和tau病理的遗传决定因素”。项目3名为“治疗帕金森症的新化合物的鉴定和测试”，由Leonard Petrucelli博士领导。核心A(管理)和核心D(神经病理学)由医学博士丹尼斯·W·迪克森领导。CORE B(临床)由医学博士Zbigniew K.Wszoiek领导。核心C(遗传学)由欧文·A·罗斯博士领导。

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.