Glycogen Synthase Kinase-3β Activity Following Repeat-Mild Traumatic Brain Injury

Date

2016-05-04

Authors

Peters, Francesca Bell
Wortman, Ryan C.
Meconi, Alicia
Christie, Brian R.

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Abstract

The tau protein is a microtubule-associated protein, which facilitates tubulin assembly into microtubules and is essential for structural integrity as well as axonal transport. When tau becomes hyperphosphorylated, it aggregates into neurofibrillary tangles disrupting proper cellular functioning. These neurofibrillary tangles are seen dispersed throughout Alzheimers diseased brains, as well as those with neurodegenerative diseases resulting from repeated traumatic brain injury. Understanding the upstream cause of tau phosphorylation is critical in the fight to develop new treatments against tau-mediated neurodegeneration. My project will look at determining the relative phosphorylation levels of tau protein following mild traumatic brain injury (mTBI), as well as quantifying activities of two tau-associated kinases, GSK3-β and CDK5, to determine if changes in these accompany changes in tau protein phosphorylation. Relative levels of tau phosphorylation and activities of GSK3-β and CDK5 will be measured by Western blotting for phosphorylation of tau residues shown to induce microtubule disassembly, and post-translational modifications shown to activate or inhibit GSK3-β and CDK5. By comparing animals that have received a single concussion with those that have received multiple concussions we will be able to determine the threshold and additive biochemical effects of multiple concussions on kinase activity and tau hyper-phosphorylation. Measuring these at different time points after the final concussion will allow us to create a better picture of what is happening biochemically within the cell to cause these changes, and observe the duration of these changes.

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Keywords

tau protein, tau phosphorylation, mild traumatic brain injury, mTBI, CDK5, concussion, GSK-3β

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