The Role of Iduna in Neuroprotection

描述(由申请人提供)：大约有250种神经-大脑和神经系统疾病。根据世界卫生组织的数据，神经系统疾病加在一起是全球死亡、残疾和生活质量下降的主要原因。这些疾病的发病率从影响数百万人的中风、癫痫和阿尔茨海默氏症，到罕见的疾病，如肌萎缩侧索硬化症和共济失调。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，细胞存活策略的发现可能会对神经系统疾病和疾病的治疗产生深远的影响，这是一个尚未得到严格研究的领域。最近，我们开发了一种策略，从预适应的神经组织中发现神经保护基因。我们已经开始鉴定的第一批基因中的一些不仅提供了对缺血和兴奋毒性损伤的保护，而且对由星形孢菌素或血清停用引发的经典的凋亡损伤具有保护作用。这非常令人兴奋，这表明有可能找到具有广泛保护性的分子，从而可能为中风甚至其他神经疾病提供治疗，如帕金森氏症、亨廷顿病或ALS。从这个筛选中，我们鉴定了一种具有神经保护作用的未知蛋白质，我们将其命名为Idna，并提出了以下目的来探索Idna的生物学功能。 目的1：Idna在对照和预适应组织中的解剖学和细胞定位是什么？目标2：伊杜纳保护神经元的死亡计划是什么？ 目的3：Idna在体内具有神经保护作用吗？ 目的4：伊杜纳的神经保护网络是什么？ 在这些研究完成后，我们将确定Idna的生物学作用及其介导的生存途径，以及确定可能受益于Idna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，以便这些途径可以用于治疗神经损伤和疾病。我们的目标是了解伊杜纳的功能，以便开发翻译疗法。

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.