Genetics and Molecular Biology of Parkinsonism

梅奥诊所的尤德尔帕金森氏病研究卓越中心是一个综合性的， 研究帕金森氏症遗传学和分子生物学的多学科中心。《中心》 利用梅奥诊所运动障碍科的临床优势以及流行病学 对帕金森氏病(PD)、路易体痴呆和衰老的纵向研究提供了 研究项目的临床材料。临床核心是一项多国努力，以确定和 帕金森病多发家系的特征及其遗传学研究。临床核心还招募和 跟踪散发性帕金森病患者，并安排进行尸检。基因核心提供了基因 家族性帕金森病的筛查和全基因组连锁研究。当许可被授予时， 样本被提交到NINDS DNA存储库。基因核心通过评估为项目4服务 转基因整合位点、拷贝数和菌株背景。神经病理学核心表演 帕金森病的死后评估，为项目提供组织学支持，并提供死后材料 通过几个不同的渠道为研究项目收集的数据。项目1建立在进展的基础上 从上一个资助期开始，证明了a-突触核蛋白基因(SCNA)在 常染色体显性，早发性帕金森病，重点研究SNCA的群体遗传学，特征 SNCA倍增(包括倍增区域内的大小和基因)，以及测量 时间和区域突触核蛋白在正常人和α-突触核病中的表达。项目2是一个 确定路易小体在正常人群中出现频率和临床表达的临床病理研究 使用梅奥医疗记录链接系统的个人，对神经元丢失的作用进行研究， 炎症和牛磺酸对临床症状的影响。项目3使用可诱导表达α-突触核蛋白的细胞系 以及线粒体毒素，如鱼藤酮，研究截短和聚集的a-突触核蛋白与 确定相互作用的蛋白质在聚集体形成中的作用和聚集体的影响的目标 蛋白酶体功能和基因表达。项目4是对转基因小鼠的多学科研究。 用a-突触核蛋白的条件表达来检验突触核病可以逆转的假设 衰老、氧化应激和转谷氨酰胺酶导致了联核症。

The Udall Center for Excellence in Parkinson's Disease Research at the Mayo Clinic is an integrated, multidisciplinary center that studies the Genetics and Molecular Biology of Parkinsonism. The Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section as well as epidemiologic and longitudinal studies of Parkinson's disease (PD), dementia with Lewy bodies and aging that provide clinical material for research projects. The Clinical Core is a multi-national effort to identify and characterize multiplex families with PD for genetic studies of PD. The Clinical Core also recruits and follows sporadic PD patients and arranges for postmortem studies. The Genetic Core provides genetic screening and performs genome wide linkage studies of familial PD. When permission is granted, samples are submitted to the NINDS DNA repository. The Genetic Core serves Project 4 by assessing transgenic integration site, copy number and strain background. The Neuropathology Core performs postmortem evaluations of PD, provides histologic support for projects and provides postmortem material collected through several different avenues for the research projects. Project 1 builds upon progress from the previous funding period demonstrating multiplication of the a-synuclein gene (SCNA) in autosomal dominant, early-onset PD and focuses on population genetics of SNCA, characterization of SNCA multiplications (including the size and genes within the multiplication regions), and measuring temporal and regional _-synuclein expression in normals and a-synucleinopathies. Project 2 is a clinicopathologic study that determines the frequency and clinical expression of Lewy bodies in normal individuals using the Mayo Medical Records Linkage System, with studies on the role of neuronal loss, inflammation and tau on clinical feaures. Project 3 uses cell lines that inducibly express a-synuclein as well as mitochondrial toxins, such as rotenone, to study truncated and aggregated a-synuclein with the goal of determining the role of interacting proteins in aggregate formation and the effects of aggregates on proteasome function and gene expression. Project 4 is a multidisciplinary study of transgenic mice with conditional expression of a-synuclein that tests the hypothesis that synucleinopathy can be reversed and that aging, oxidative stress and transglutaminase contribute to the synucleinopathy.