Caspase-12 is a molecule with a death-wish. Found only in people of African descent, this protein shuts down our body's immune system, opening the door to potentially lethal infections.
In a groundbreaking new study published in the prestigious journal Nature this week, the team that first discovered the role of caspase-12 in humans has now uncovered the mechanism by which it sabotages us, allowing researchers to develop methods to counter its damaging effects.
Caspase-12 is found in around 20% of people of African descent, but was entirely lost from all other ethnicities around 60,000 years ago.
"It's a mystery why only African populations retained this enzyme," says Dr. Maya Saleh, a medical scientist in the Critical Care Division at the MUHC and assistant professor in the Department of Medicine at McGill University. It's possible that in Africa the protein could once have had a protective function fighting autoimmune diseases or perhaps parasites, like malaria; today caspase-12 provides no benefit to those who carry it, and often leaves the body more vulnerable to life-threatening infections and sepsis ('septic shock'). "Only by investigating the mechanisms by which caspase-12 works can we hope to inhibit its destructive effects," says Dr. Saleh.
Dr. Saleh and a research team from Merck and the La Jolla Institute for Allergy and Immunology in San Diego conducted laboratory experiments using mice deficient in the caspase-12 gene.
"We discovered that caspase-12 blocks the body's inflammatory response to infection by blocking the activity of another useful enzyme," says Dr. Saleh. "It's kind of like the bad leading the good astray." Dr. Saleh's discovery is a major step forward and will allow researchers to develop treatments that may help strengthen the immune system of those people unfortunate enough to have the caspase-12 gene product.
This research was funded by a fellowship from the Canadian Institutes for Health Research (CIHR), the MUHC and McGill University to Dr. Saleh.
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