Protein Accumulation in Traumatic Brain Injury

Douglas H. Smith, Kunihiro Uryu, Kathryn E. Saatman, John Q. Trojanowski, Tracy K. McIntosh

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Traumatic brain injury (TBI) is one of the most devastating diseases in our society, accounting for a high percentage of mortality and disability. A major consequence of TBI is the rapid and long-term accumulation of proteins. This process largely reflects the interruption of axonal transport as a result of extensive axonal injury. Although many proteins are found accumulating after TBI, three have received particular attention; β-amyloid precursor protein and its proteolytic products, amyloid-β (Aβ) peptides, neurofilament proteins, and synuclein proteins. Massive coaccumulations of all of these proteins are found in damaged axons throughout the white matter after TBI. Additionally, these proteins form aggregates in other neuronal compartments and in brain parenchyma after brain trauma. Interestingly, TBI is also an epigenetic risk factor for developing neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Here, the similarities and differences of these accumulations with pathologies of neurodegenerative diseases will be explored. In addition, the potential deleterious roles of protein accumulations on functional outcome and progressive neurodegeneration following TBI will be examined.

Original languageEnglish
Pages (from-to)59-72
Number of pages14
JournalNeuroMolecular Medicine
Volume4
Issue number1-2
DOIs
StatePublished - 2003

Bibliographical note

Funding Information:
This work was supported, in part, by grants from the National Institute of Neurological Disorders and Stroke (P50-NS08803 and RO1-NS40978 to T.K.M.); the National Institute of General Medical Sciences (RO1-GM34790 to T.K.M.), National Institutes of Health (NIH) grants NS38104 (to D.H.S.), AG12527 (to D.H.S.), AG11542 (to J.Q.T.), AG-10124 (to J.Q.T.), and NS-45131 (to K.E.S.); a Merit Review grant from the Veterans Administration (to T.K.M.); and a Veterans Administration-DOD consortium Merit Review grant (to T.K.M.).

Keywords

  • APP
  • Accumulation
  • Amyloid precursor protein
  • Amyloid-β
  • Brain trauma
  • DAI
  • Diffuse axonal injury
  • Neurofilament proteins
  • Synuclein proteins
  • TBI
  • Traumatic brain injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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