MGH/MIT MORRIS UDALL CENTER OF EXCELLENCE IN PD RESEARCH

麻省总医院/麻省理工学院莫里斯尤德尔 PD 研究卓越中心

• 批准号: 7911991
• 负责人: ANNE B YOUNG
• 金额: $ 1.2万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911991
• 关键词: Address; Arts; Autopsy; Bioinformatics; Brain; Caring; Cell Culture Techniques; Charge; Clinical; Corpus striatum structure; Data; Data Analyses; Disease; Fluorescence; Future; Gene Transfer; Genes; Genetic Screening; Human; Image; Lead; Lewy Bodies; Mammalian Cell; Parkinson Disease; Parkinsonian Disorders; Pathology; Patients; Reagent; Research; Research Personnel; Rodent Model; Scientist; System; Technology; Toxic effect; Training; Viral Vector; alpha synuclein; dopaminergic neuron; laser capture microdissection; molecular pathology; programs; protein protein interaction; relating to nervous system; response; synuclein; yeast genetics

DESCRIPTION (provided by applicant): The MGH/MIT Morris Udall Center of Excellence in PD Research is taking a broad, collaborative and interactive approach to the study of Parkinson's disease. The Projects address critical questions concerning the selective vulnerability of dopamine neurons, the mechanism and consequences of Lewy body formation and alpha-synuclein aggregation, the neural systems consequences of parkinsonism and synuclein pathology, and molecular approaches for modifying this pathology. These issues will be explored using a range of systems, from yeast genetics, to mammalian cell culture, to rodent models to human postmortem material. The Center incorporates state-of-the-art technologies including high throughput yeast genetic screens to identify modifiers of synuclein aggregation and toxicity, viral vector gene transfer to study factors in mammalian cell culture and rodent models, multi-unit tetrode recordings to study striatal plasticity, fluorescence lifetime imaging to study protein-protein interactions, and laser capture microdissection and gene arrays to study transcriptional dysregulation. The Center has a Clinical and Training Core that provides care to patients with Parkinson's disease, gathers data on clinical features of the disease and response to therapy, solicits brain donations for neuropathological study, and trains outstanding clinician scientists to be future leaders in the field. The Center also has a Bioinformatics Core that serves to integrate and analyze data across the projects, and facilitate sharing of the information. The Administrative Core is charged with management of the Center and facilitating the sharing of information, ideas, and reagents among the investigators and with other components of the Udall Centers consortium. The investigators of the MGH/MIT Center are dedicated to a program of collaborative and interactive studies which will lead to better treatments for people with Parkinson's disease.

描述（由申请人提供）： MGH/MIT MORRIS UDALL PD研究卓越中心正在采用广泛，协作和互动的方法来研究帕金森氏病。这些项目解决了有关多巴胺神经元选择性脆弱性的关键问题，Lewy身体形成的机制和后果和α-核蛋白聚集的机制和后果，帕金森主义和甘蓝蛋白病理学的神经系统后果，以及分子方法，用于修饰这种病理。这些问题将使用从酵母遗传学到哺乳动物细胞培养，再到啮齿动物模型再到人类验尸材料的一系列系统。该中心结合了最先进的技术，包括高吞吐酵母遗传筛选，以识别突触核蛋白聚集和毒性的修饰符，病毒载体基因转移到哺乳动物细胞培养和啮齿动物模型中的研究因素，多单位tetrode模型，多单位tetrode记录以研究纹状体可塑性，促进蛋白质量和捕获蛋白质的相互作用和lase蛋白生产率，并捕获了型号的生产率，并失调。该中心有一个临床和训练核心，为帕金森氏病的患者提供护理，收集有关该疾病的临床特征的数据和对治疗的反应，为神经病理学研究提供大脑捐赠，并培训杰出的临床医生科学家成为该领域的未来领导者。该中心还具有生物信息学核心，该核心核心可以整合和分析整个项目的数据，并促进信息共享。行政核心负责管理中心，并促进调查人员以及Udall Centers联盟的其他组件之间的信息，想法和试剂的共享。 MGH/MIT中心的研究人员致力于协作和互动研究计划，该计划将为帕金森氏病患者提供更好的治疗方法。

项目成果

Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity.

• DOI: 10.1038/ng.337
• 发表时间: 2009-03
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Yeger-Lotem, Esti;Riva, Laura;Su, Linhui Julie;Gitler, Aaron D.;Cashikar, Anil G.;King, Oliver D.;Auluck, Pavan K.;Geddie, Melissa L.;Valastyan, Julie S.;Karger, David R.;Lindquist, Susan;Fraenkel, Ernest
• 通讯作者: Fraenkel, Ernest

[18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

[18F]-多巴正电子发射断层扫描成像在早期非帕金青少年帕金森病中的应用。

• DOI: 10.1002/mds.10133
• 发表时间: 2002
• 期刊: Movement disorders : official journal of the Movement Disorder Society
• 作者: Pal,PramodK;Leung,Joanne;Hedrich,Katya;Samii,Ali;Lieberman,Abraham;Nausieda,PaulA;Calne,DonaldB;Breakefield,XandraO;Klein,Christine;Stoessl,AJon
• 通讯作者: Stoessl,AJon

Formation of toxic oligomeric alpha-synuclein species in living cells.

• DOI: 10.1371/journal.pone.0001867
• 发表时间: 2008-04-02
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Outeiro TF;Putcha P;Tetzlaff JE;Spoelgen R;Koker M;Carvalho F;Hyman BT;McLean PJ
• 通讯作者: McLean PJ

Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson's disease.

人脑中 α-突触核蛋白、parkin 和泛素羧基末端水解酶 L1 mRNA 的表达：与家族性帕金森病相关的基因。

• 发表时间: 2000
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Solano,SM;Miller,DW;Augood,SJ;Young,AB;PenneyJr,JB
• 通讯作者: PenneyJr,JB

Pathophysiology of Tourette's syndrome: striatal pathways revisited.

抽动秽语综合症的病理生理学：重新审视纹状体通路。

• DOI: 10.1016/s0387-7604(03)90002-7
• 发表时间: 2003
• 期刊: Brain & development
• 影响因子: 1.7
• 作者: Saka,Esen;Graybiel,AnnM
• 通讯作者: Graybiel,AnnM