Investigators will study animal models to learn how deadly prions—misfolded proteins that are infectious in animals and humans—travel from immune sites in the body to the brain.
Prions aggregate and produce deadly infections in the brain. They are responsible for mad cow disease in cattle, scrapie in sheep, and fatal Creutzfeldt-Jakob disease and kuru in humans. In some cases, humans have developed the disease by eating infected beef or through blood transfusions or organ transplants. It takes a long time following exposure for cognitive and motor symptoms to develop, because prions must first travel from peripheral sites in the body to the brain. There, they infect brain cells, generating additional copies of the misfolded protein in a relentlessly progressive domino effect that spreads the infection to cells throughout the brain.
How do prions travel from the digestive tract and other sites in the body and pass into the brain? Scientists have found that organs involved in immune cell development and maturation—such as lymph nodes, spleen, and bone marrow—actually serve as the prions’ staging area, where they propagate. Subsequently, researchers speculate, peripheral nerves that stimulate these organs serve as conduits that transport prions to the spinal cord and brain. Investigators will test these hypotheses by using a novel technology that takes advantage of mice genetically engineered to produce prions that are fluorescent and will glow green under the microscope.
First, researchers will analyze the distribution of fluorescent prions in the intestine, spleen, lymph nodes, and involved peripheral nerves. Next, they will analyze dissemination of prions within the spleen using a cell transplantation technique. Finally, they will study prions that are selectively generated in specific immune cells and nerve cells, to analyze the processes involved in transporting prions from the immune system to the brain.
Significance: Learning how prions travel to the brain could lead to development of methods for blocking this process and preventing deadly prion infection in the brain.