The Role of Iduna in Neuroprotection

Iduna 在神经保护中的作用

• 批准号: 7275931
• 负责人: VALINA L. DAWSON
• 金额: $ 39.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275931
• 关键词: Address; Affect; Alzheimer' s Disease; American; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Apoptosis; Apoptotic; Area; Ataxia; Attention; Cause of Death; Cell Death; Cell Survival; Cells; Cessation of life; Cultured Cells; Disease; Epilepsy; Future; Genes; Goals; Healed; Huntington Disease; Incidence; Individual; Infarction; Injury; Ischemia; Learning; Mediating; Medical; Modeling; Names; Neurologic; Neurons; Parkinson Disease; Pathway interactions; Pharmacologic Substance; Play; Proteins; Quality of life; Range; Rare Diseases; Regulation; Research Personnel; Resistance; Role; Serum; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Staurosporine; Stroke; Tissues; Transgenic Mice; Withdrawal; World Health Organization; cell injury; cost; cytotoxicity; disability; excitotoxicity; healing; in vivo; mouse model; nervous system disorder; neuroprotection; novel; preconditioning; programs; protein expression; protein protein interaction; relating to nervous system

DESCRIPTION (provided by applicant): There are approximately 250 neurological - brain and nervous system - disorders. Combined, neurologic disorders are the leading cause of death, disability and loss of quality of life worldwide according to the World Health Organization. The incidence of these disorders ranges from stroke, epilepsy and Alzheimer's, which affect millions, to rare diseases such as amyotrophic lateral sclerosis and ataxia's. To address the problem of brain and nervous system disorders investigators have focused attention on describing cell injury mechanisms. However, discovery of cell survival strategies could have profound impact on the treatment of neurologic disorders and disease and is an area that has not yet been rigorously investigated. Recently we developed a strategy to discover neuroprotective genes from preconditioned neural tissue. Some of the first genes we have begun to characterize provide protection not only against ischemic and excitotoxic injury but are protective against classic apoptotic injury triggered by staurosporin or serum withdrawal. This is very exciting, suggesting that it might be possible to find molecules that are broadly protective and therefore might provide treatment for stroke and perhaps even for other neurologic disorders such as Parkinson's disease, Huntington's disease or ALS. From this screen we identified a protein of unknown function that is potently neuroprotective that we have named Iduna and proposed the following aims to explore the biologic function of Iduna. Aim 1: What is the anatomical and cellular localization of Iduna in control and preconditioned tissues? Aim 2: What are the death programs against which Iduna protects neurons? Aim 3: Is Iduna neuroprotective in vivo? Aim 4: What is the neuroprotective network of Iduna? On completion of these studies we will have identified the biologic actions of Iduna and the survival pathways it mediates, as well as, identified potential disease targets that might benefit from expression of Iduna. Our long-term goal is to understand novel enodgenous survival pathways so that these pathways can be exploited for the treatment of neurologic injury and disease. The goal is to understand the function of Iduna so that translational therapy can be developed.

描述（由申请人提供）：大约有 250 种神经系统 - 大脑和神经系统 - 疾病。根据世界卫生组织的数据，神经系统疾病是全世界死亡、残疾和生活质量下降的主要原因。这些疾病的发病率包括影响数百万人的中风、癫痫和阿尔茨海默氏症，以及肌萎缩侧索硬化症和共济失调等罕见疾病。为了解决大脑和神经系统疾病的问题，研究人员将注意力集中在描述细胞损伤机制上。然而，细胞生存策略的发现可能对神经系统疾病的治疗产生深远的影响，并且是一个尚未经过严格研究的领域。最近，我们开发了一种策略，从预处理的神经组织中发现神经保护基因。我们已经开始表征的一些第一批基因不仅提供针对缺血性和兴奋性毒性损伤的保护，而且还针对星形孢菌素或血清撤退引发的经典细胞凋亡损伤提供保护。这是非常令人兴奋的，表明有可能找到具有广泛保护作用的分子，从而可以治疗中风，甚至可能治疗其他神经系统疾病，如帕金森病、亨廷顿病或肌萎缩侧索硬化症。从这个筛选中，我们鉴定了一种功能未知的蛋白质，该蛋白质具有有效的神经保护作用，我们将其命名为 Iduna，并提出以下目标来探索 Iduna 的生物学功能。 目标 1：Iduna 在对照组织和预处理组织中的解剖学和细胞定位是什么？目标 2：Iduna 保护神经元免受哪些死亡程序影响？ 目标 3：Iduna 在体内具有神经保护作用吗？ 目标 4：Iduna 的神经保护网络是什么？ 完成这些研究后，我们将确定 Iduna 的生物学作用及其介导的生存途径，并确定可能受益于 Iduna 表达的潜在疾病靶点。我们的长期目标是了解新的内源性生存途径，以便利用这些途径来治疗神经损伤和疾病。目标是了解 Iduna 的功能，以便开发转化疗法。