Researchers from University of Texas Medical Branch at Galveston have successfully unveiled a potential key molecular mechanism that may be responsible for chronic brain damage as a result of traumatic brain injury.
The critical brain protein tau, also associated with the pathogenesis of Alzheimer’s disease and a variety of other neurodegenerative conditions, is known to create deposits in the form of abnormal aggregates. There are two forms of this abnormal deposition — neurofibrillary tangles and oligomers. Under normal circumstances, tau is important for the health of brain cells, but toxic deposition in the form of oligomers can impair normal metabolic functioning of healthy tau by clumping and attaching to oligomer units.
Researchers at the University of Texas Medical Branch at Galveston identified that traumatic brain injuries induce the formation of tau oligomers. The experiments conducted on laboratory rats by novel antibodies revealed that tau oligomers develop within 4 hours after initial injury and may persist for a period of up to 2 weeks. Since oligomers also have the capability to affect the normal tau proteins, it can be safely assumed that the lasting brain damage due to brain injury is mediated by tau oligomers.
The results of this remarkable discovery were published online in the Journal of Biological Chemistry.
Lead author of the study, Bridget Hawkins, commented:
“Although people have given some attention to the formation of neurofibrillary tangles after traumatic brain injury, we were the first to look at tau oligomers, because we have an antibody that allows us to separate them out and see how much of the total tau is the toxic species. We saw that it’s a substantial amount — enough to play an important role in the effects of traumatic brain injury.”
University of Texas Medical Branch at Galveston researchers hypothesized that the long term consequences of traumatic brain injury can be controlled if the process of tau oligomerization can be stopped. The research team suggested that antibodies can be used to label tau oligomers (these antibodies are developed as vaccines to prevent a variety of neurodegenerative diseases.
Associate professor at UTMB and senior author on the paper, Rakez Kayed, commented:
“We have antibodies that can specifically target these tau oligomers without interfering with the function of healthy tau. This is a new approach — we’re starting by targeting them in animals — but we hope to eventually humanize these antibodies for clinical trials.”
The long term consequences of traumatic brain injury mediated by tau oligomers are deficits in memory, disruption in the normal sleep –wake cycle, and seizure activity.