Day 69: Prions want to eat our brains. But what ARE they?

Thanks to research on zebrafish, scientists now understand the normal function of the prion proteins that, when maligned, cause brain-wasting diseases.

Surely I’m not alone in those moments when the burger is a little too pink, and I’m thinking: this could be the one. This could be the burger that’s harboring those mysterious little prions, and they’ll worm their way into my brain and start eating. I’ll forget things, insignificant, random things at first, as the little buggers munch increasingly big holes … until eventually I’ll be — well, dead. 

If there’s good news, it’s that my understanding of the disease process has been flawed. Prion diseases don’t actually involve an eating of the brain. (Where did I even get that?) Prion diseases begin when a normal protein misfolds, and then replicates like crazy in the brain, eventually choking out whole neurons. Prions are linked to transmissible “spongiform” encephalopathies (brain diseases) including Kuru and Creutzfeldt-Jacob disease in humans, scrapie in sheep, and mad cow disease in cattle. “Spongiform” because that’s what the brain looks like — a sponge — in a person who has died, usually within a couple of months. 

The diseases are thought to be rare. Unless prions are lurking in the brains of a lot of beef-eaters (that’s my fear; prions can be dormant for decades), about one person in a million will get a prion-caused disease. Some people get it from contaminated Human Grown Hormone, some from eating infected animals. In some cases, the ailment will arise within the infected person, either from a genetic mutation or because a normal protein simply went awry.

Until now, scientists haven’t known why prion proteins are produced by our bodies in the first place. Previous experiments in genetically modified mice had failed to yield conclusive evidence, as animals lacking prion proteins seemed perfectly healthy. But a study on a little fish, published earlier this month in the open access journal PLoS ONE, has finally revealed a clue about prion protein’s role.

Zebrafish embryos don't develop properly when scientists block the function of prion proteins.

Lead author Edward Málaga-Trillo, a biologist at the University of Konstanz in Germany, and his colleagues injected zebrafish eggs with morpholinos, DNA-like molecules that prevent the normal production of prion protein. The treated zebrafish embryos were unable to develop normally, and eventually died. The proteins in the fish embryos normally found at cell-to-cell contact sites disappeared, rendering these cells unable to communicate and carry out the differentiation program that shapes the major structures of the body, including the nervous system.

Their findings suggest that prion protein indeed plays a beneficial role — it helps cells communicate with one another during embryonic development.

“We were then able to prove that [prion protein] serves as a glue element, bringing cells together and keeping them in contact,” explains co-author Gonzalo Solis (all of the co-authors hail from the University of Konstanz). “When two neighboring cells make contact, they become able to exchange important signals that affect the function of a tissue in the body.”

Although the work doesn’t offer a cure for prion diseases, the authors say they’ve assembled the first pieces of a complex puzzle, which may widen our understanding of the diseases and provide hope for an eventual solution.

Sources: The study and a Eurekalert press release about the findings. Also, a pinch of Wikipedia. A lengthy, interpretive article is available at PLoS ONE.