Science: A matter of life and death

Most animals have prions - proteins that can cause fatal nervous diseases. So why do we have them in the first place?

Hamsters have them. So do goats, sheep, mink, mice and man. In fact, in just about every animal where scientists have looked, prions can be found. These are the mysterious proteins that are responsible for a range of strange nervous diseases, including BSE in cattle and CJD in humans. Now the biggest mystery of all - why we need prions in the first place - may have been solved.

A Cambridge biochemist, David Brown, believes he has evidence to suggest that animals need prions as protection against that highly necessary, but potentially lethal, activity known as breathing oxygen. All living things, save for a few lowly bacteria, need oxygen, but dealing in this vital currency of respiration risks exposure to the chemical's highly reactive form, called superoxide. Dr Brown suggests that the reason why prions are so common is because they are a crucial line of defence against superoxide.

"All animals need oxygen and as a consequence of using oxygen they produce superoxide, which is basically oxygen with an extra electron stuck on to it," says Dr Brown. "This is quite dangerous because the electron can shoot off and damage cells. Anything to make this superoxide less harmful is of benefit."

If the prion protein does serve this function, Dr Brown has solved a mystery that goes back several decades, when scientists first linked prions to such deadly nervous diseases as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cows and Creutzfeldt-Jakob disease (CJD) in humans. Prions are directly involved, and may even be the cause of these strange illnesses, yet for all the research that has been done on them, no one has yet understood why we need such proteins, if they are so potentially fatal.

The original name for a prion was protease-resistant protein (PrP) because it could exist in a form that was not broken down by digestive enzymes. In fact, this was how it came to the attention of scientists. Isolating the protein soon led to finding out its primary structure - the sequence of 253 amino acids that made up the protein chain. Then scientists found that the PrP gene responsible for the human protein resides on chromosome 20 and is highly "conserved" between different species, meaning that it is virtually identical between one animal and the next. It indicated that it must serve some common function dating back many millions of years in evolutionary history - a key indication that the normal form of the PrP protein has a pretty important role.

For 20 or more years, however, the nature of this function remained elusive. The most that scientists were able to do was to categorise the nature of the illnesses resulting from defects in the protein. For example, small mutations in the gene can result in a wide variety of inherited diseases. Substituting one amino acid for another at the 102nd link in the protein chain, for instance, results in Gerstmann-Straussler-Scheinker disease in humans - an unusual brain disorder. Substituting the 200th amino acid causes a type of CJD seen in Libyan Jews, and changing the 129th amino acid can cause the highly distressing condition known as fatal familial insomnia, which causes people to die after months of being incapable of catching even a minute's sleep.

But it is the non-inherited, transmissible forms of prion disease - notably BSE - that have caused the most intense interest. A curiosity is that the amino acids of PrP protein are exactly the same as normal PrP in both healthy cows and those with BSE, as they are in healthy sheep and sheep with scrapie. Stanley Prusiner, the California University scientist who won a Nobel Prize for his prion hypothesis, believes the disease is caused by deformed versions of the protein (deformed, that is, in its three-dimensional shape) triggering a similar deformity in normal, healthy versions of the protein.

Yet this still does not explain why we need prions. Dr Brown, who leads a team in Cambridge's department of biochemistry, discovered what he thinks is the crucial clue to the protein's normal function when he found that it can strongly bind to copper. Proteins that bind to this metal could have a role as an enzyme involved in coping with superoxide. Other enzymes, called superoxide dismutases, are known to do this and the PrP protein may perform a similar task, Dr Brown says. "Usually copper in a protein can be effective in bringing this about. Like wires, they can shuttle electrons around. Probably what happens in this case is that the electron is shuttled on to the prion protein itself and oxidises the prion protein. A particular amino acid in the protein can become oxidised and is quite stable. The cell can get rid of the superoxide in this way."

The evidence for this comes from experimental results to be published in the Biochemical Journal. Dr Brown manufactured pure PrP protein by inserting the mouse PrP gene into bacteria that grew in fermentation. He found evidence that the protein, when bound up with copper, acted like a superoxide dismutase enzyme - to destroy the harmful molecule. He repeated the experiment with chicken PrP protein and found it, too, did the same.

Dr Brown believes the protein has an especially important role to play at the junctions - synapses - between brain cells, moping up superoxide before it has a chance to damage these all-important connections within the central nervous system. "The implications are that we now know what the normal protein does. The main aspect of prion diseases is that the normal protein is turned into this pathological form that causes the disease; we are now at a point where we can try to find out about the abnormal form."

Knowing the normal role of the PrP protein in the body should shed light on what happens when the abnormal prion protein appears. It may be that the body loses its prime defence in the brain against superoxide. Or it could be that a build-up of defective prions causes a dangerous build- up of copper.

Although Dr Brown's research says nothing about the mysterious nature of how a prion "infects" other prions, he seems to have come close to answering one of the more enduring problems of prion disease. In man or mouse, prions are there to stop oxygen burning us up.

Have you tried new the Independent Digital Edition apps?
Arts and Entertainment

ebooksNow available in paperback
Arts and Entertainment

ebooks
Arts and Entertainment

film
Arts and Entertainment
Chvrches lead singer Lauren Mayberry in the band's new video 'Leave a Trace'

music
Arts and Entertainment

music
Arts and Entertainment
Home on the raunch: George Bisset (Aneurin Barnard), Lady Seymour Worsley (Natalie Dormer) and Richard Worsley (Shaun Evans)

TV review
Arts and Entertainment

TV
Arts and Entertainment
Strictly Come Dancing was watched by 6.9m viewers

Strictly
Arts and Entertainment
NWA biopic Straight Outta Compton

film
Arts and Entertainment
Natalie Dormer as Margaery Tyrell and Lena Headey as Cersei Lannister in Game of Thrones

Game of Thrones
Arts and Entertainment
New book 'The Rabbit Who Wants To Fall Asleep' by Carl-Johan Forssen Ehrlin

books
Arts and Entertainment
Calvi is not afraid of exploring the deep stuff: loneliness, anxiety, identity, reinvention
music
Arts and Entertainment
Edinburgh solo performers Neil James and Jessica Sherr
comedy
Arts and Entertainment
If a deal to buy tBeats, founded by hip-hop star Dr Dre (pictured) and music producer Jimmy Iovine went through, it would be Apple’s biggest ever acquisition

album review
Arts and Entertainment
Paloma Faith is joining The Voice as a new coach

TV
Arts and Entertainment
Dowton Abbey has been pulling in 'telly tourists', who are visiting Highclere House in Berkshire

TV
Arts and Entertainment

TV
Arts and Entertainment
Patriot games: Vic Reeves featured in ‘Very British Problems’
TV review
Arts and Entertainment
film review
Arts and Entertainment
Summer nights: ‘Wet Hot American Summer: First Day of Camp’
TVBut what do we Brits really know about them?
Arts and Entertainment
Dr Michael Mosley is a game presenter

TV review
Latest stories from i100
Have you tried new the Independent Digital Edition apps?
SPONSORED FEATURES

ES Rentals

    Independent Dating
    and  

    By clicking 'Search' you
    are agreeing to our
    Terms of Use.

    A nap a day could save your life - and here's why

    A nap a day could save your life

    A midday nap is 'associated with reduced blood pressure'
    If men are so obsessed by sex, why do they clam up when confronted with the grisly realities?

    If men are so obsessed by sex...

    ...why do they clam up when confronted with the grisly realities?
    The comedy titans of Avalon on their attempt to save BBC3

    Jon Thoday and Richard Allen-Turner

    The comedy titans of Avalon on their attempt to save BBC3
    The bathing machine is back... but with a difference

    Rolling in the deep

    The bathing machine is back but with a difference
    Part-privatised tests, new age limits, driverless cars: Tories plot motoring revolution

    Conservatives plot a motoring revolution

    Draft report reveals biggest reform to regulations since driving test introduced in 1935
    The Silk Roads that trace civilisation: Long before the West rose to power, Asian pathways were connecting peoples and places

    The Silk Roads that trace civilisation

    Long before the West rose to power, Asian pathways were connecting peoples and places
    House of Lords: Outcry as donors, fixers and MPs caught up in expenses scandal are ennobled

    The honours that shame Britain

    Outcry as donors, fixers and MPs caught up in expenses scandal are ennobled
    When it comes to street harassment, we need to talk about race

    'When it comes to street harassment, we need to talk about race'

    Why are black men living the stereotypes and why are we letting them get away with it?
    International Tap Festival: Forget Fred Astaire and Ginger Rogers - this dancing is improvised, spontaneous and rhythmic

    International Tap Festival comes to the UK

    Forget Fred Astaire and Ginger Rogers - this dancing is improvised, spontaneous and rhythmic
    War with Isis: Is Turkey's buffer zone in Syria a matter of self-defence – or just anti-Kurd?

    Turkey's buffer zone in Syria: self-defence – or just anti-Kurd?

    Ankara accused of exacerbating racial division by allowing Turkmen minority to cross the border
    Doris Lessing: Acclaimed novelist was kept under MI5 observation for 18 years, newly released papers show

    'A subversive brothel keeper and Communist'

    Acclaimed novelist Doris Lessing was kept under MI5 observation for 18 years, newly released papers show
    Big Blue Live: BBC's Springwatch offshoot swaps back gardens for California's Monterey Bay

    BBC heads to the Californian coast

    The Big Blue Live crew is preparing for the first of three episodes on Sunday night, filming from boats, planes and an aquarium studio
    Austin Bidwell: The Victorian fraudster who shook the Bank of England with the most daring forgery the world had known

    Victorian fraudster who shook the Bank of England

    Conman Austin Bidwell. was a heartless cad who carried out the most daring forgery the world had known
    Car hacking scandal: Security designed to stop thieves hot-wiring almost every modern motor has been cracked

    Car hacking scandal

    Security designed to stop thieves hot-wiring almost every modern motor has been cracked
    10 best placemats

    Take your seat: 10 best placemats

    Protect your table and dine in style with a bold new accessory