The Role of Iduna in Neuroprotection

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，神经系统疾病是世界范围内导致死亡、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，到肌萎缩性侧索硬化症和共济失调症等罕见疾病。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，这是一个尚未得到严格研究的领域。最近，我们开发了一种从预处理神经组织中发现神经保护基因的策略。我们已经开始描述的一些第一批基因不仅提供对缺血性和兴奋性损伤的保护，而且还提供对staurosporin或血清停药引发的经典凋亡损伤的保护。这是非常令人兴奋的，这表明有可能找到具有广泛保护作用的分子，从而可能为中风甚至其他神经系统疾病（如帕金森病、亨廷顿病或肌萎缩侧索硬化症）提供治疗。从这个筛选中，我们发现了一种功能未知的蛋白质，它具有强大的神经保护作用，我们将其命名为Iduna，并提出了以下目标来探索Iduna的生物学功能。

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.