Genetics and Molecular Biology of Parkinsonism

简介（由申请人提供）：梅奥诊所的尤德尔帕金森病卓越研究中心是一个综合性的多学科研究项目，专注于“帕金森病的遗传学和分子生物学”。尤德尔中心利用梅奥诊所运动障碍科的临床优势，对帕金森氏病（PD）进行纵向研究，重点关注家族性帕金森氏症的临床遗传学，拥有庞大的帕金森氏病脑库，并致力于帕金森氏病的研究和教育。尤德尔中心的所有组成部分都设在佛罗里达州的杰克逊维尔，尽管明尼苏达州罗切斯特的核心资源，特别是生物医学统计部门将被使用。Mayo基金会的教育资源，包括赞助的系列研讨会和PD及其他神经退行性疾病的研究生教育课程也被利用。该建议具有高度创新性和原创性，因为它解决了tau和a-突触核蛋白这两个具有惊人相似性的分子之间有趣的相互作用，这两个分子都是帕金森病发病机制的关键因素。临床、遗传和病理研究将充分利用尤德尔中心研究人员的固有优势，以及多年来由于研究人员的热情投入而建立起来的独特的临床、遗传和病理资源，以更好地了解PD及相关疾病。该中心还引进了互补研究领域的知名研究人员(博士。Rademakers和Petrucelli)致力于了解tau与PD之间的关系，以及tau定向疗法如何转化为PD和帕金森病的新疗法。该中心将有三个项目和四个核心，其总体主题是了解tau蛋白在帕金森病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型帕金森病基因”，由Rosa Rademakers博士领导。项目2名为“帕金森病中a-突触核蛋白和tau蛋白病理的遗传决定因素”，由Dennis W. Dickson博士领导。项目3名为“鉴定和测试治疗帕金森病的新化合物”，由Leonard Petrucelli博士领导。核心A（行政管理）和核心D（神经病理学）由Dennis W. Dickson博士领导。核心B（临床）由Zbigniew K. Wszoiek博士领导。核心C（遗传学）由Owen A. Ross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.