• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

'Brain Disease Proteins Linked to Stem Cells'

Posted on: Tuesday, 31 January 2006, 12:00 CST

By JOHN VON RADOWITZ

Prion proteins, the infectious agent behind mad cow disease and CJD, appear to perform a vital function maintaining stem cells, new research has shown. Scientists have been puzzled about prions since finding that they were involved in the spread of devastating animal and human brain diseases.

Mis-shapen prion proteins are thought to be responsible for BSE, or mad cow disease, its human equivalent variant Creutzfeldt- Jakob disease, scrapie in sheep, and a number of similar disorders.

All these diseases, known as transmissible spongiform encephalopathies or TSEs, are marked by a build-up of wrongly folded prions. The rogue proteins cause normal prions they come into contact with to adopt the same dangerous change in shape, triggering a chain reaction.

In the brain, the consequences are disastrous. Misfolded prions destroy neurons and leave the brain full of holes, like a sponge, leading to disability and death.

Since prions, or 'PrP', are potentially so deadly, scientists have wondered why nature has preserved them.

The proteins are found in many mammals and throughout healthy human bodies, especially in the brain.

Yet early research indicated that they performed no useful function.

In 1993, researchers created a line of genetically engineered 'knock-out' mice lacking the prion gene.

The mice were unable to make prions, but surprisingly appeared to show no ill-effects. The only difference about them was that they were incapable of contracting TSEs - an advantage which, according to the laws of natural selection, should have got rid of prions a long time ago.

Yesterday scientists reported new findings which suggest that nature kept prions for a very good reason. They seem to play a key role in maintaining healthy supplies of stem cells - immature cells which are programmed by the body to develop into a range of different tissues.

The US discovery could have important implications for research exploring the possibility of using stem cells to treat human diseases.

Dr Chengcheng Zhang, from the Whitehead Institute in Cambridge, Massachusetts, was studying blood-forming stem cells in mouse foetal tissue when he spotted that prions were abundant on the surface of the cells.

'I found that, while not all blood cells with PrP on their surface were stem cells, any cell that lacked PrP was definitely not a stem cell,' he said.

Dr Zhang teamed up with graduate researcher Andrew Steele, who specialises in prions, to investigate the possible role of PrP in stem cell biology.

The two scientists took bone marrow from 'knock-out' mice lacking prions and transferred it to normal mice whose own marrow had been neutralised by radiation.

The second group of mice grew new blood and immune system cells from stem cells in the transplanted bone marrow. However, all the cells lacked prions.

Bone marrow from these mice was then transferred to another group of irradiated mice. This process was repeated again and again, as the researchers transplanted bone marrow from one group of mice to another.

Soon they noticed that, with each subsequent transplant, the stem cells in the bone marrow began to lose their ability to reconstitute themselves.

Eventually the scientists ended up with mice whose bone marrow stem cells were completely unable to generate new blood cells.

But when the experiment was repeated with bone marrow containing abundant prions, each transplant was as good as the next. At no point did the bone marrow stem cells lose their potency.

Dr Susan Lindquist, one of the scientists who took part in the research, said, 'For years we've wondered why evolution has preserved this protein, what positive role it could possibly be playing. With these findings, we have our first answer. This is the first clear indication we have of a beneficial role for it in a living animal. Now we need to discover its molecular mechanism.'

The findings were reported yesterday in the journal Proceedings of the National Academy of Sciences.

Source: Western Mail

More News in this Category