PILOT: BRAIN PROTEIN SUMOYLATION FOR NEUROPROTECTION

The goal of this research project is to perform experiments that will determine whether or not a process in cells called SUMOylation reduces the effects of traumatic brain injury (TBI). Briefly, under certain circumstances cells can attach a ¿SUMO molecule¿ to proteins through a series of biochemical steps. Previous research indicates protein SUMOylation can protect cells from destruction when they are stressed, as occurs during TBI and strokes. To test whether or not SUMOylation reduces the effects of TBI, we will use genetically modified mice that carry extra gene copies of an enzyme. By having additional copies of the enzyme, mice express higher cellular levels of SUMOylated proteins. We hypothesize that elevation in the amount of SUMOylated proteins will ¿protect¿ cells from destruction, reducing the severity of TBI, and result in these mice exhibiting better performance on behavioral tests compared to mice that express normal levels of protein SUMOylation. At the present time there are no known drugs that stimulate protein SUMOylation, but if protein SUMOylation is beneficial, we will explore mechanisms that might increase protein SUMOylation as a means of protecting the brain after TBI.