Innate and Adaptive Immunity in Parkinson Disease

帕金森病的先天性和适应性免疫

• 批准号: 8936250
• 负责人: DAVID G. STANDAERT
• 金额: $ 32.08万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936250
• 关键词: Anxiety; Basic Science; Biological Models; Bradykinesia; Brain; CD4 Positive T Lymphocytes; Clinical; Collaborations; Communities; Community Outreach; Complement; Data; Dementia; Development; Disease; Disease Progression; Education and Outreach; Elements; Environment; Fostering; Functional disorder; Future; Gap Junctions; Goals; Grant; HLA-DR Antigens; Immune system; Immunoglobulins; Impaired cognition; Infiltration; Inflammatory; LRRK2 gene; Lead; Ligands; Mediation; Mental Depression; Motor; Mus; Myeloid Cell Activation; Myeloid Cells; National Institute of Neurological Disorders and Stroke; Natural Immunity; Nature; Neurodegenerative Disorders; Parkinson Disease; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Phase; Population; Positron-Emission Tomography; Pre-Clinical Model; Predisposition; Process; Production; Proteins; Recommendation; Reporting; Research Personnel; Resources; Risk Factors; Role; Signal Transduction; Sleep Disorders; Staging; Substantia nigra structure; Symptoms; TNFRSF5 gene; Testing; Therapeutic; Tissues; Tremor; Vision; adaptive immunity; alpha synuclein; base; chemokine; cytokine; equilibration disorder; gastrointestinal; genome wide association study; human disease; human subject; member; neuroimmunology; neuroinflammation; neuron loss; neuroprotection; non-motor symptom; novel; pars compacta; perineural; pre-clinical; programs; public health relevance; restoration; success; symposium; therapeutic target; urinary

 DESCRIPTION (provided by applicant): The development of neuroprotective strategies for PD is a vital unmet need. Despite remarkable advances in the last fifteen years in the understanding of pathobiological mechanisms in PD, there are no known therapies available that slow the progression or alter the course of PD. The systemic nature of PD suggests new pre-clinical approaches are needed in order to identify pathways and associated therapeutics that might slow the progression of disease. As stated in the Conference and Recommendations Report to NINDS Council (PD2014), "the community of investigators focused on PD now strives to create therapies that meaningfully slow or stop the disease mechanisms that underlie all symptoms of PD". Neuroinflammation is increasingly recognized as a critically important element of PD pathogenesis. The vision for this P20 Exploratory Grant is to create the team, environment, and capability to explore innate and adaptive immunity in PD. Currently, there are no Udall Centers of Excellence that focus on understanding neuroinflammatory mechanisms in PD. These studies will require a team with a combination of specialized expertise in neuroimmunology and neurodegenerative disorders. We request support to foster the development of new collaborations and to develop critical data both in PD subjects as well as in recently developed pre-clinical models of PD. The investigative team includes two established investigators in PD (Drs. David Standaert and Andrew West), and an established investigator from the field of neuroimmunology (Dr. Etty "Tika" Benveniste). We will explore neuro-inflammatory signaling, particularly the actions of myeloid cells, in pre-clinical models of PD as well as early human disease. It is expected that success in these exploratory studies will lead to the development of a future Udall Center of Excellence dedicated to understanding the roles of the innate and adaptive immune system in PD, with emphasis on pursuing points of therapeutic mediation and novel neuroprotection strategies.

 描述（由申请方提供）：PD神经保护策略的开发是一项重要的未满足需求。尽管在过去的15年中，在对PD的病理生物学机制的理解方面取得了显着的进展，但没有已知的治疗方法可以减缓PD的进展或改变PD的病程。PD的全身性质表明需要新的临床前方法来确定可能减缓疾病进展的途径和相关治疗方法。正如提交给NINDS理事会的会议和建议报告（PD 2014）中所述，“专注于PD的研究者社区现在正在努力创造有意义地减缓或停止PD所有症状背后的疾病机制的疗法”。 神经炎症越来越多地被认为是PD发病机制的一个至关重要的因素。该P20探索性资助的愿景是创建团队，环境和能力，以探索PD的先天性和适应性免疫。目前，还没有Udall卓越中心专注于了解PD的神经炎症机制。这些研究将需要一支具有神经免疫学和神经退行性疾病专业知识的团队。我们请求支持，以促进新合作的发展，并开发PD受试者以及最近开发的PD临床前模型的关键数据。研究团队包括两名PD领域的知名研究者（大卫·斯坦德特博士和安德鲁·韦斯特博士）和一名神经免疫学领域的知名研究者（埃蒂“提卡”·本维尼斯特博士）。我们将探讨神经炎症信号，特别是骨髓细胞的行动，在临床前模型的PD以及早期人类疾病。预计这些探索性研究的成功将导致未来Udall卓越中心的发展，该中心致力于了解先天性和适应性免疫系统在PD中的作用，重点是追求治疗调解和新的神经保护策略。