The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains
AuthorCorrigan, F; Pham, CLL; Vink, R; Blumbergs, PC; Masters, CL; van den Heuvel, C; Cappai, R
Source TitleBRAIN RESEARCH
Document TypeJournal Article
CitationsCorrigan, F., Pham, C. L. L., Vink, R., Blumbergs, P. C., Masters, C. L., van den Heuvel, C. & Cappai, R. (2011). The neuroprotective domains of the amyloid precursor protein, in traumatic brain injury, are located in the two growth factor domains. BRAIN RESEARCH, 1378, pp.137-143. https://doi.org/10.1016/j.brainres.2010.12.077.
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C1 - Journal Articles Refereed
The amyloid precursor protein (APP) is known to increase following traumatic brain injury (TBI). This increase in levels of APP may be deleterious to outcome due to the production of neurotoxic Aβ. Conversely, this upregulation may be beneficial as cleavage of APP via the alternative non-amyloidogenic pathway produces the soluble α form of APP (sAPPα), which is known to have many neuroprotective and neurotrophic functions. Indeed it has previously been shown that treatment with sAPPα following a diffuse injury in rats improves outcome. However, the exact location within the sAPPα molecule which contains this neuroprotective activity has yet to be determined. The sAPPα peptide can consist of up to 6 domains, with the main isoform in the brain missing the 4th and 5th. Of the remaining domains, the D1 and D6a domains seem the most likely as they have been shown to have beneficial actions in vitro. This present study examined the effects of in vivo posttraumatic administration via an intracerebroventricular injection of the D1, D2 and D6a domains of sAPPα on outcome following moderate-impact acceleration TBI in rats. While treatment with either the D1 or D6a domains was found to significantly improve motor and cognitive outcome, as assessed on the rotarod and Y maze, treatment with the D2 domain had no effect. Furthermore axonal injury was reduced in D1 and D6a domain treated animals, but not those that received the D2 domain. As the D1 and D6a domains contain a heparin binding region while the D2 domain does not, this suggests that sAPPα mediates its neuroprotective response through its ability to bind to heparin sulfate proteoglycans.
KeywordsNeurology and Neuromuscular Diseases; Nervous System and Disorders
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