CENC - Tau Conformation and Phosphorylation in mTBI

 描述（由申请人提供）： 创伤性脑损伤（TBI）是军事人员和平民人群死亡和发病的主要原因。据报告，它也是工业化国家45岁以下年龄组死亡和残疾的主要原因。在伊拉克和阿富汗战争中幸存下来的士兵中，创伤性脑损伤占伤亡人数的比例比美国近代历史上任何其他战争都要大。此外，在沃尔特里德医院接受评估的患者中，闭合性头部损伤明显多于其他穿透性损伤。大多数轻度TBI（mTBI）患者在一年内恢复正常表现，但中度和重度脑损伤更为复杂，后果持久。现在，mTBI被认为是平民和军人群体的主要健康问题。重复性损伤可能导致痴呆样症状，患者可能会出现记忆丧失、攻击性、混乱和抑郁。目前在美国甚至全世界很少有专门针对mTBI的临床试验，并且通常正在研究的药物是针对其他病症开发的，并且迄今为止显示出非常小的功效，这可能是由于缺乏对构成大脑对mTBI的次级应答的分子机制的了解。这些众多而复杂的机制可能在事件发生后持续数月甚至数年，患者的结局取决于这些机制以及原始损伤的类型、严重程度和位置。为了有效的急性和长期治疗mTBI，需要在分子和细胞水平上充分理解支配神经元修复和神经元损伤和死亡的生物学事件。与脑中神经元稳定性相关的tau蛋白参与阿尔茨海默病和其他神经退行性疾病，并且现在被认为在脑对阿尔茨海默病和其他神经退行性疾病的反应中是重要的。

 DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major cause of mortality and morbidity among both military personnel and the civilian population. It is also reported to be the leading cause of death and disability in the under-45 age group in industrialized countries. Among the soldiers who survive conflicts in Iraq and Afghanistan, traumatic brain injuries account for a larger proportion of thei casualties than in any other war in recent US history. Furthermore, among patients evaluated at the Walter Reed Hospital, closed head injuries significantly outnumber other penetrating injuries. Most individuals with a mild TBI (mTBI) return to normal performance within a year, but moderate and severe brain injuries are more complex and have long-lasting consequences. mTBI is now recognized to be a major health concern for both civilian and military populations. Repetitive injuries may result in dementia like symptoms where the patient may experience memory loss, aggression, confusion and depression. There are very few current clinical trials in the US or even worldwide which are specifically addressing mTBI, and typically the drugs under investigation were developed for other conditions and have shown very little efficacy thus far, presumably due to the lack of knowledge of the molecular mechanisms which constitute the brains' secondary response to mTBI. These numerous and complex mechanisms may persist for months and even years after the event, and the outcome for the patient depends on these, as well as the type, severity and location of the original injury. For effective acute and long-ter treatment of mTBI, the biological events that govern neuronal repair and neuronal damage and death need to be fully understood at the molecular and cellular level. The tau protein which is associated with neuronal stability in the brain, is involved in Alzheimer's disease and other neurodegenerative diseases, and is now recognized to be important in the brain's response to