New research conducted by the Stony Brook University School of Medicine, Stony Brook, NY, suggests that p53, the most commonly mutated gene in cancer, may also play a role in the development of ischemic stroke. The study’s findings highlight the function of the gene in activating necrosis, triggering oxidative stress and ischemia. Ute Moll, MD, professor of pathology, reiterates the findings. “We identified an unexpected and critical function of p53 in activating necrosis: In response to oxidative stress in normal healthy cells, p53 accumulates in the mitochondrial matrix and triggers the opening of the PTP pore at the inner mitochondrial member, leading to collapse of the electrochemical gradient and cell necrosis.” Researchers report that they observed a physical interaction between p53 and the PTP regulator Cyclophylin D (CypD). The action occurs in cultured cells and in ischemic stroke in mice, Moll notes.
The researchers add that results from their study model indicate that when the p53-CypD complex is blocked from forming by using Cyclosporine-A type inhibitors, the brain tissue is strongly protected from necrosis and stroke is prevented. “The data also suggest that acute temporary blockade of the destructive p53-CypD complex with clinically well-tolerated Cyclosporine A-type inhibitors may lead to a therapeutic strategy to limit the extend of an ischemic stroke in patients,” Moll says.
Source: Stony Brook University School of Medicine