Various recent studies have reported a link between head trauma and and an increased risk of Alzheimer's disease, but why this might be has been a matter of speculation. In this month’s Journal of Neurochemistry, Tracy McIntosh, Michelle LaPlaca, and colleagues provides the first description of how poly(ADP-ribose) polymerase (PARP), which identifies damaged DNA for repair by other enzymes, fluctuates following head injury. Such insights into the processes by which DNA repair mechanisms are inhibited following head injury are likely to shed light on how acute CNS injury might accelerate age-related genomic damage and contribute to apoptotic processes and neurodegenerative disease.

McIntosh and colleagues induced head injuries in adult rats and monitored the damage to DNA and the levels of PARP for seven days. At 30 minutes following injury, despite the relative lack of damaged DNA, PARP levels were already elevated. Conversely, at seven days, despite the high levels of damaged DNA, PARP levels had returned to baseline. Together with previous evidence, these data suggest that, in the longer term, PARP synthesis is inhibited by apoptosis-associated mechanisms. In particular, it is thought that PARP, which is supposed to identify a site needing repair and then disassociate itself, is cleaved by caspase-3 and gets “stuck” at the DNA, blocking the site from repair enzymes.—Hakon Heimer


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Primary Papers

  1. . Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat. J Neurochem. 1999 Jul;73(1):205-13. PubMed.