Normal 'mad cow' protein helps keep cells talking, study suggests
Last Updated: Monday, March 9, 2009 | 8:10 PM ET
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A group of German researchers may have figured out why a protein that can turn rogue and cause fatal illnesses such as mad cow disease exists in large quantities inside cows, humans and other animals.
The protein — known as the "prion" protein or PrP — appears to help cells communicate with each other when an embryo is developing, said a paper published Monday in the journal PloS Biology by a group of researchers at University of Konstanz in Germany.
"What we see PrP doing in the fish embryo … may be analogous to what it does in the mammalian brain, which is what may go wrong during prion diseases," biologist Edward Malaga-Trillo, who led the study, said in an email to CBCNews.ca.
Diseases such as mad cow disease in cows and Creutzfeldt-Jakob disease in humans have been traced back to rogue, altered versions of the prion protein. But up until now, researchers have been unsure what normal versions of the protein are supposed to do.
Those normal proteins are the "starting ingredient" for prion diseases. When prion proteins fold abnormally, they clump together into groups called plaques that lead to brain damage. The misfolded prions multiply by turning normal prions "bad."
In previous studies, mice engineered so they were unable to produce the normal prion protein seemed mostly normal.
However, in the recent study led by University of Konstanz biologist Edward Malaga-Trillo, zebrafish embryos that could not make the prion protein didn't develop normally and eventually died.
A closer study of mouse, fish and fruit fly cells showed that the prion protein caused certain proteins to accumulate at the interface where two cells touched each other.
"We were then able to prove that PrP serves as a glue element, bringing cells together and keeping them in contact," co-author Dr. Gonzalo Solis said in a statement.
"When two neighbouring cells make contact, they become able to exchange important signals that affect the function of a tissue in the body."
Specialized cells
Those signals seem to help cells co-ordinate and move to the right places when they reach a stage of development where they must transform from identical stem cells to different kinds of specialized cells, such as brain cells or skin cells.
A puzzling question is why the problems seen in the zebrafish weren't seen in the mice used in earlier studies.
The authors suggest that the mice may have other proteins that compensate for the missing protein. That may be partly due to a known weakness in the "knockout" method used to stop the production of the prion protein in the mice, which was different from the "knockdown" method used to block the production of the prion protein in the zebrafish, Malaga-Trillo said.
There have been some hints in the past as to the role of the prion protein. A study published last May by researchers at Rockefeller University suggested that prions prevent the brain from overreacting to electrical and drug-induced stimulation.
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