CENC - Tau Conformation and Phosphorylation in mTBI

 描述(由申请人提供)： 创伤性脑损伤是造成军人和平民死亡和发病的主要原因。据报道，它也是工业化国家45岁以下人群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，创伤性脑损伤在他们伤亡中所占的比例比美国近代史上任何其他战争中都要大。此外，在沃尔特里德医院接受评估的患者中，闭合性头部损伤的数量远远超过其他穿透性损伤。大多数轻度颅脑损伤(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，并具有长期后果。现在，MTBI已被认为是平民和军人的主要健康问题。反复损伤可能会导致类似痴呆症的症状，患者可能会经历记忆力丧失、攻击性、困惑和抑郁。目前在美国甚至世界范围内，专门针对mTBI的临床试验很少，通常情况下，正在研究的药物是针对其他疾病开发的，到目前为止显示出的疗效很小，可能是因为缺乏对mTBI构成大脑二次反应的分子机制的了解。这些众多而复杂的机制可能会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了解控制神经元修复和神经元损伤和死亡的生物学事件。Tau蛋白与大脑中神经元的稳定性有关，与阿尔茨海默氏症和其他神经退行性疾病有关，现在被认为在大脑对

 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