Genetics and Molecular Biology of Parkinsonism

帕金森病的遗传学和分子生物学

• 批准号: 8724250
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 141.05万
• 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/8724250
• 关键词: Address; Affect; Age; Amyotrophic Lateral Sclerosis; Area; Autopsy; Brain; CSF1R gene; Candidate Disease Gene; Clinic; Clinical; Code; Collaborations; Collection; Complement; DNA; DNA Sequence; Databases; Diagnosis; Diffuse; Disease; Doctor of Philosophy; Education; Educational Status; Experimental Designs; Family; Family history of; Family member; Florida; Foundations; Frontotemporal Dementia; Gender; Gene Expression; Gene Frequency; Gene Mutation; General Population; Genes; Genetic; Genetic Determinism; Genetic Variation; Genotype; Haplotypes; Housing; In Vitro; Individual; Inherited; Joints; Leukoencephalopathy; Lewy Body Disease; Logistic Regressions; Longitudinal Studies; Messenger RNA; Microtubules; Minnesota; Minor; Molecular Biology; Movement Disorders; Mutation; Nature; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Parkinson Disease; Parkinsonian Disorders; Pathogenesis; Pathogenicity; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Population; Prevalence; Principal Investigator; Progressive Supranuclear Palsy; Protocols documentation; Regression Analysis; Research; Research Personnel; Resources; Risk; Role; Rosa; Series; Site; Tauopathies; Technology; Testing; Translating; Variant; Work; alpha synuclein; base; case control; cohort; disability; disorder risk; gene discovery; genetic epidemiology; genetic pedigree; genome sequencing; innovation; insertion/deletion mutation; mRNA Expression; member; neuropathology; next generation; novel; population based; proband; programs; protein aggregation; protein expression; statistics; synucleinopathy; tau Proteins; tau aggregation

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.

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，重点关注“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，对帕金森病 (PD) 进行纵向研究，重点关注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帕金森病研究和教育的坚定机构承诺。尤德尔中心的所有组成部分均位于佛罗里达州杰克逊维尔，但将使用明尼苏达州罗彻斯特的核心资源，特别是生物医学统计部。梅奥基金会的教育资源，包括赞助的研讨会系列和关于帕金森病和其他神经退行性疾病的研究生水平教育课程也得到利用。该提案具有高度创新性和原创性，因为它解决了两个具有惊人相似性的分子（tau 和 a-突触核蛋白）之间有趣的相互作用，这两种分子都与帕金森病发病机制中的关键因素密切相关。拟议的临床、遗传和病理研究利用了尤德尔中心研究人员的固有优势以及由于研究人员热衷于更好地了解 PD 和相关疾病而多年来建立的独特的临床、遗传和病理资源。该中心还汇集了互补研究领域的知名研究人员（Rademakers 博士和 Petrucelli 博士），以了解 tau 蛋白如何与 PD 相关，以及 tau 蛋白导向疗法如何转化为 PD 和帕金森病 tau 病的新疗法。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 tau 病中的作用。项目 1 题为“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 题为“帕金森病中 a-突触核蛋白和 tau 病理学的遗传决定因素”，由医学博士 Dennis W. Dickson 领导。项目 3 题为“治疗帕金森症的新型化合物的识别和测试”，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 Dennis W. Dickson 领导。核心 B（临床）由医学博士 Zbigniew K. Wszoiek 领导。核心 C（遗传学）由 Owen A. Ross 博士领导。