Morris K. Udall Centers of Excellence for Parkinson's Disease Research (P50)

莫里斯·尤德尔帕金森病研究卓越中心 (P50)

• 批准号: 8932807
• 负责人: Ted M. Dawson
• 金额: $ 200.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8932807
• 关键词: ABL1 gene; Acute; Affect; Animal Model; Area; Biological Markers; Brain; Case Study; Cell Death; Cells; Cessation of life; Chronic; Clinical; Community Outreach; Complex; Data Set; Discipline; Disease; Disease Marker; Disease Progression; Dopaminergic Cell; Economics; Etiology; Evaluation; Event; Family; Financial cost; Fostering; Gene Expression Profile; Genes; Genetic Translation; Genetically Engineered Mouse; Goals; Human; Individual; Institution; Investigation; LRRK2 gene; Lead; Medical; Modeling; Monitor; Morbidity - disease rate; Mus; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Dysfunction; Neuronal Injury; Parkinson Disease; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phosphorylation; Phosphotransferases; Preventive; Process; Proteome; Research; Research Personnel; Resources; Role; Signal Transduction; Staging; Structure; Syndrome; System; TNFRSF5 gene; Technology; Training; Tyrosine; United States; Work; alpha synuclein; arm; base; c-abl Proto-Oncogenes; clinical Diagnosis; cost; data sharing; disability; dopaminergic neuron; improved; insight; multidisciplinary; parkin gene/protein; programs; progression marker; public health relevance; response; social; synuclein; transmission process

 DESCRIPTION (provided by applicant): Parkinson's disease (PD) is relentlessly progressive and despite effective symptomatic therapy in the early stages of the illness most patients have substantial morbidity and disability. There is an urgent need to understand the etiology and pathogenesis of PD so that more effective symptomatic therapies and ultimately preventive therapies can be developed. Our hypothesis is that a-synuclein, parkin and LRRK2 contribute to a complex signaling network that results in the pathogenesis of Parkinson's Disease and related disorders. The center will approach this hypothesis in a multidisciplinary manner. The center represents a multi-disciplinary, mechanistic approach involving interactive, productive investigators with complementary areas of expertise who have long been committed to studies of neurodegenerative diseases. Our center will integrate diverse advanced technologies within the center to accelerate discovery. It will work collaboratively within the Udall Center Network to accelerate discovery of disease, new therapies and disease and progression biomarkers. Through the integration of the activities of the various disciplines, the interrelationships will result in a greater scientific contribution than could be achieved if each project or center investigation were pursued individually. The Johns Hopkins Udall Center will serve as a local and national resource for PD research including broad sharing of data and clinical and biospecimen resources and fostering community outreach activities. We will provide and coordinate training of young investigators in the pathogenesis and study of Parkinson's disease and Parkinson's syndromes. The Johns Hopkins Udall Center is focused on understanding the interrelationship between parkin (Project 1), the most common cause of autosomal recessive PD, -synuclein (Project 2), which is causal in sporadic PD and LRRK2 (Project 4), the most common cause of autosomal dominant PD and to use our discoveries to develop disease and progression markers (Project 3) and ultimately new therapies. The insights into how these three genes interact in the pathogenesis of PD and the discovery of biomarkers would not be possible without the Udall Center structure as it enables the evaluation of these major causes of PD and the ability to evaluate findings in each arm of PD to elucidate common pathways if they exist as these may provide the best opportunities for comprehensive new therapies and biomarkers. We believe that our multi-disciplinary approach has the capacity to produce unique information concerning the mechanisms of neuronal injury in animal models of PD that will lead to a better understanding of the function and the role of -synuclein, parkin, and LRRK2 in normal and pathophysiologic processes related to PD.

 描述（由申请人提供）：帕金森病 (PD) 呈持续性进展，尽管在疾病早期阶段进行了有效的对症治疗，但大多数患者仍存在严重的发病率和残疾，迫切需要了解帕金森病的病因和发病机制，以便了解帕金森病的病因和发病机制。我们的假设是，α-突触核蛋白、parkin 和 LRRK2 构成了一个复杂的信号网络，导致帕金森病和相关疾病的发病机制。该中心将以多学科的方式来实现这一假设。该中心代表了一种多学科、机械的方法，涉及具有互补专业领域的互动、富有成效的研究人员，他们长期致力于神经退行性疾病的研究。该中心将在尤德尔中心网络内协同工作，以加速发现。 疾病、新疗法以及疾病和进展生物标志物的发现，通过整合各个学科的活动，相互关系将产生比单独进行每个项目或中心研究更大的科学贡献。尤德尔中心将作为帕金森病研究的地方和国家资源，包括广泛共享数据以及临床和生物样本资源，并促进社区外展活动。我们将为年轻研究人员提供和协调帕金森病和帕金森病发病机制和研究的培训。约翰·霍普金斯大学 Udall 中心致力于了解 Parkin（项目 1）（常染色体隐性遗传 PD 的最常见原因）、α-突触核蛋白（项目 2）（导致散发性 PD 的原因）和 LRRK2（项目 4）之间的相互关系，常染色体显性帕金森病的最常见原因，并利用我们的发现来开发疾病和进展标记物（项目 3），并最终深入了解这三种疗法。基因在帕金森病的发病机制中相互作用，如果没有尤德尔中心结构，就不可能发现生物标志物，因为它能够评估帕金森病的这些主要原因，并能够评估帕金森病每个分支的发现，以阐明共同的途径（如果存在）因为这些可能为全面的新疗法和生物标志物提供最佳机会，我们相信我们的多学科方法有能力产生有关帕金森病动物模型神经损伤机制的独特信息，从而更好地了解其功能。和角色α-突触核蛋白、parkin 和 LRRK2 在与 PD 相关的正常和病理生理过程中的作用。