Canadian researchers identify new prion protein
Updated Fri. Aug. 17 2007 9:05 AM ET

Canadian Press

TORONTO -- Canadian scientists have discovered a new prion protein, a finding which could both help illuminate how prion diseases like Creutzfeldt-Jakob or mad cow disease destroy the brain as well as offer clues as to what is at play with other neurodegenerative diseases.

The scientists, led by Dr. David Westaway at the University of Alberta's Centre for Research in Neurodegenerative Diseases, report that they have isolated a prion protein called Shadoo, which is found in the brain cells of mice, humans and probably other mammals.

The protein appears to protect neurons, they reported in an article in the Embo Journal (the acronym stands for the European Molecular Biology Organization). In mice infected with a prion disease, Shadoo starts to disappear, suggesting a lack of this protein contributes to the damage done by the disease, Westaway said in an interview from Edmonton.

He said there is no evidence Shadoo triggers disease itself, but that it may "aid and abet" the disease process.

Shadoo is only the third prion protein to have been discovered in the 20-plus years since prions - misfolded proteins - have been recognized as an agent of disease. It was long thought the originally discovered prion protein, called PrP, was the sole such protein. But within the last five years or so another, known as Doppel, was also identified.

Dr. Neil Cashman, a leading prion researcher, said the Shadoo finding both answers some fundamental questions about prion diseases and provides a lead that should be explored about Shadoo's possible role in other neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS or Lou Gehrig's disease.

"How neurons are killed in prion diseases has been a mystery for years," explained Cashman, a researcher at the University of British Columbia and scientific director of PrioNet Canada, a federally funded network of prion researchers.

This discovery of Shadoo and of the fact that it disappears in the disease process suggests that the loss of the protein leaves neurons vulnerable to assault or degeneration, he said.

"If a protective agent has been xed out of the figure - which is Shadoo - it would make sense that those neurons would not tolerate insults to the degree that normal neurons would."

And if that's true in CJD it may also be true in other, more common afflictions of the brain, Cashman said. "It is a logical extension that Shadoo is playing a role, not only in experimental scrapie" - the sheep prion disease - "but perhaps in Alzheimer's disease, Parkinson's disease, ALS. There's a long list."

Westaway, though, said it's still too soon to speculate about a broader role for Shadoo in neurodegenerative diseases.

"It would be great if it turned out that way. But I think it's a little bit of a stretch now," he said.

Instead, Westaway sees the work as answering some of the mysteries that have surrounded prion diseases, caused when normal, healthy prion proteins misfold and spur a similar aberrant effect in other prion proteins.

This triggers a chain of events that leads to disease - such as the erosion of brain tissue in CJD. But why good prion proteins go bad and how bad prion proteins (which are typically just called prions) do the damage they do is still not well understood.

Nor has there been a broad understanding of the normal functioning of healthy prion proteins and the protective role they play.

"Our understanding of the prion protein comes out of its role in disease rather than discovering the prion protein as a neuro-protective protein and then realizing: Hey wait a minute, it can become misfolded," Cashman said.

"So the original surge of research dealing with the prion protein ... focused on the mistake of nature aspect of this protein, rather than its true activity," he said, adding that the Westaway paper is "the latest instalment in figuring out what the prion protein does to protect cells."

"It's kind of an 'Aha!' moment to read this paper," Cashman said.

"Whether it can be applied in medicine or not, I think it's very possible it could be, but we don't know that yet. Or at least not yet for sure. So I put it in the scientific puzzle solving category, in which it has a lot of significance."

Westaway said the research continues to try to figure out why Shadoo disappears in disease, and whether this new prion protein can also take an aberrant, misfolded form.


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