How prions invade the brain

According to a study published November 29 in the open access journal, the transmission of prions to the brain does not occur by direct transmission across the blood-brain barrier. PLOS Pathogens by Annika Keller and Adriano Aguzzi from the University Hospital Zurich and their colleagues. As noted by the authors, information on how prions enter the brain could lead to the development of effective strategies for the prevention of neurodegeneration, even after an infection outside the nervous system.

Prion diseases or transmissible spongiform encephalopathies (TSE) are incurable brain diseases caused by changes in the prion protein. Prions can be transmitted through contaminated food, surgical instruments and blood. The transmission of prions has caused the outbreak of kuru in humans and bovine spongiform encephalopathy in cattle, which has caused a variant of Creutzfeldt-Jakob disease in humans . In addition, the injection of prion-contaminated hormones has caused hundreds of TSE cases. In order to develop drugs to prevent the spread of prions in the brain after exposure to food or medical procedures, it is necessary to understand how prions propagate from the entry site to the brain.

In this new study, the researchers checked whether prions present in the blood could enter the brain through the blood vessels. To do this, they used genetically modified mice with a highly permeable blood-brain barrier: a network of closely spaced blood vessels and tissue that prevents harmful substances from reaching the brain. . Genetically modified and unmodified mice had similar survival rates after prion infection. These surprising findings suggest that the passage of prions across the blood-brain barrier may not be relevant to the development of the disease. These new findings, combined with past discoveries, suggest that prions probably reach the brain by moving along the nerves of other parts of the body, similar to rhabdoviruses and herpesviruses.

"Studies on mice with a permeable BBB add to the conjecture that prion propagation from the periphery to the brain does not occur through direct transitions through BBB," adds Keller. "In addition to their importance for the basic understanding of neuroinvasion by prions, these findings may also affect the possibility of developing effective post-exposure prophylaxis for prion diseases, which can prevent neurodegeneration even after they have been prionised. an extraneural infection has already occurred "

Explore further:
The adaptation of prions between species depends on the environment of prion replication

More information:
Keller A, Nuvolone M, Abakumova I, Chincisan A, Reimann R, Avar M, et al. (2018) The pathogenesis of prions is not altered in a mouse strain with a permeable hematoencephalic barrier. PLoS Pathog 14 (11): e1007424. doi.org/10.1371/journal.ppat.1007424