PRION proteins that play a key role in diseases such as BSE in cattle and vCJD in humans might have a benign alter ego. In their normal form they may help the development of a healthy nervous system.
No one quite knows what function normal prions serve in healthy tissue. Now Andrew Steele at the Whitehead Institute in Cambridge, Massachusetts, and Jason Emsley at Massachusetts General Hospital have found that prions act as a type of molecular 鈥済as pedal鈥� for the rudimentary stem cells that turn into the different types of neurons in the brain.
Mice genetically engineered to produce no prions take longer to develop new neurons, while those hyperloaded with normal prions develop new neurons at a much faster rate than their normal counterparts. All the mice ultimately develop the same number of new neurons however, suggesting that other systems might also govern the speed of neural cell development, Steele says.
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The same team discovered earlier that stem cells from bone marrow rely on prions to bump up their population after radiation has depleted them (麻豆传媒, 4 February, p 21).
鈥淭ogether, these results show pretty conclusively that the very unique properties of prions somehow help moderate that other very mysterious entity, stem cells,鈥� says Jiyan Ma, a prion researcher at Ohio State University in Columbus, who did not participate in the research. 鈥淭he trick is now to figure out what exactly that relationship is.鈥�
鈥淭he unique properties of prions somehow moderate that other very mysterious entity, stem cells鈥�
Both Ma and Steele believe that prions may act as a type of signal transducer on the membrane of growing neural cells, enabling the cells to coordinate their efforts via biochemical messengers. The absence of prions in this system wouldn鈥檛 necessarily cause complete failure because of other, similarly assigned proteins, but it might result in minor disturbances such as erratic sleep patterns, which occur in mice that produce no prions.
The finding might help shed some light on the first few links in the chain reaction of vCJD, one of the most puzzling types of neurodegenerative disease. Rogue prions are unique in the way they spread disease. If a few of them from meat infected with BSE, for example, come into contact with healthy prions they can persuade them to take on the same misfolded configuration.
Malfunctioning prions in the system that controls cell development could scramble the instructions for rebuilding and replenishing the brain, says Ma, and this may lead to the spongy brain formation associated with BSE and vCJD. Research now needs to focus on these signalling systems to figure out exactly where prions fit in, he says.
