A Novel Neuroprotective Protein, Thorase

描述(申请人提供)：大约有250种神经性“大脑和神经系统”障碍。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。其中一些基因不仅提供了对缺血和兴奋性毒性损伤的保护，而且还保护了对细胞凋亡和血清撤除的保护。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，因此可能提供新的治疗策略。从这个筛选中，我们鉴定了一个基因，Thorase，编码一种功能未知的蛋白质，具有强大的神经保护作用，并提出了以下目的来探索Thorase的生物学功能。目的1：Thorase的解剖学和细胞定位是什么？目的2：Thorase的生物学功能是什么？新目标3：Thorase在神经保护中的作用是什么？目的4：Thorase在体内具有神经保护作用吗？在这些研究完成后，我们将确定Thorase的生物学作用及其介导的生存途径，以及确定可能受益于Thorase表达的潜在疾病靶点。我们的长期目标是了解Thorase的功能，以便开发翻译治疗。与公共卫生相关。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。预适应放大了人体的自然宿主防御系统，提供了深刻而广泛的保护。了解预适应信号级联反应对于开发具有缺血性损伤风险的患者的药物治疗以及治疗慢性神经退行性疾病具有巨大的潜力。该项目试图了解一种新发现的预适应蛋白质是如何保护大脑的，以开发新的治疗方法。

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 these genes provide protection not only against ischemic and excitotoxic injury but are also protective against apoptosis and serum withdrawal. This is very exciting, suggesting that it might be possible to find molecules that are broadly protective and therefore might provide new treatment strategies. From this screen we identified a gene, Thorase, encoding a protein of unknown function that is potently neuroprotective that and proposed the following aims to explore the biologic function of Thorase. Aim 1: What is the anatomical and cellular localization of Thorase? Aim 2: What is the biologic function of Thorase? New Aim Aim 3: What is the role of Thorase in Neuroprotection? Aim 4: Is Thorase neuroprotective in vivo? On completion of these studies we will have identified the biologic actions of Thorase and the survival pathways it mediates, as well as, identified potential disease targets that might benefit from expression of Thorase. Our long-term goal is to understand the function of Thorase so that translational therapy can be developed. PUBLIC HEALTH RELEVANCE. Combined, neurologic disorders are the leading cause of death, disability and loss of quality of life worldwide according to the World Health Organization. Preconditioning amplifies the human body's natural host defense system to provide profound and broad protection. Understanding the preconditioning signal cascade has tremendous potential to develop pharmaceutical treatments of patients at risk for ischemic injury and perhaps for treating chronic neurodegenerative diseases. This project seeks to understand how a newly discovered protein in preconditioning protects the brain in order to develop new therapeutic treatments.