Protein Modification: A Proposed Mechanism for the Long-Term Pathogenesis of Traumatic Brain Injury
Abstract
Traumatic brain injury (TBI) is a major cause of long-term disability. Acute TBI prompts a constellation of dysfunctional processes, collectively known as secondary injury mechanisms. A hallmark secondary injury in TBI is a prolonged imbalance in calcium homeostasis, resulting in a dramatic influx of calcium into brain cells. This influx elicits the generation of damaging reactive oxygen species. Protein carbonylation and citrullination are pathological post-translational modifications that can result from intracellular calcium overload. These modifications have been proposed to play a role in neurodegenerative disorders, including Alzheimers disease, and multiple sclerosis. Both carbonylation and citrullination can contribute to ongoing dysfunction, either through direct loss of protein function or via immune-based mechanisms where proteins specifically modified by citrullination become targeted by the adaptive immune system. This work investigated carbonylation and citrullination in a rodent model of TBI. We have identified specific regions and cell types susceptible to these modifications following TBI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 04, 2015
- Accession Number
- AD1012716
Entities
People
- Rachel C. Lazarus
Organizations
- Uniformed Services University of the Health Sciences