CENC - Tau Conformation and Phosphorylation in mTBI

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 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