Nogo this time

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Helena Tobin
BIOLS final-year undergraduate

After a term of an arts/science course called Practical Journalism, I was inspired to enter the Young Science Writer competition, sponsored by the Daily Telegraph and the chemical company BASF.

This established competition - supported since 1987 by the British Association for the Advancement of Science - was inundated with over 400 entries. Consequently, I was surprised to hear that my entry, an article on the Nogo inhibitor of neuronal regeneration, had reached the 'celebrity panel round', consisting of Dr Laura Garwin (physical sciences editor of Nature), Professor Lewis Wolpert, Glenwyn Benson (the BBC's head of science), and John Hampton of BASF.

Writing the article had proved to be an interesting opportunity to interview some of the leading research groups in the country, although in hindsight the hardest part was choosing the subject matter. As for the competition, unfortunately and true to its name, the Nogo article did not advance to the final round.

However, with the knowledge that I reached the last 60 entries and achieved a Highly Commended certificate, I walk away with the experience to do better in the competition next year.

Helena's article...

Warning: This is a Nogo area

Next time you cut or graze your skin, admire how your body goes about the repair of the damage. It is an intricate job carried out by the maintenance department of your organs, tissue and peripheral nervous system that is often take for granted.

Subsequently, when a thousand people every year in the UK injure the nerves in their spinal cord, along with the many others who suffer Alzheimer and stroke damage to the neural system of the brain, we wonder why the maintenance departments in these areas of the body are stopped from repairing and preventing the permanent disability caused by these injuries.

The edge of this puzzle was completed back in the 1980s when it was discovered that nerves from the brain and spinal cord, collectively known as the central nervous system, could grow on cells from other parts of the body, but not in their natural cellular environment. This suggested that a nerve in the brain or spinal cord has the potential to grow but its development is halted by stop signals.

Since then further progress has been made with the puzzle, with many of the inhibitory molecules being isolated and characterised, and yet one major perpetrator has remained elusive until now.

A research group from SmithKline Beecham have recently been involved in a project to collar the mysterious inhibitory molecule given the name "Nogo", traced in other animals but never identified in humans. By using clues in cow DNA sequences, which are the instructions for the building of Nogo proteins, a computerised database of similar human DNA sequences was searched to produce an identity parade of likely suspects. From this line-up, the human Nogo gene sequence was isolated, cloned and inserted into cells that would manufacture the protein.

The definitive evidence confirming suspicions that the newly produced protein was indeed Nogo came when a plate of branching neurons were stopped from extending by the addition of the suspect protein. This proved that Nogo, encoded by the guilty DNA message, was a "potent inhibitor of neurite outgrowth. Steve Moore, the team leader of the Nogo project, is clearly pleased with this discovery, and said that "It's always exciting and gratifying to get the first functional data".

Nogo is expressed in the neighbours of nerves called oligodendrocytes. These are cells in the brain and spinal cord that form a myelin sheath, which is an electrical insulating layer of cells that wraps around nerve fibres in the same way that plastic covers wires. The Nogo molecules discovered in this layer of cells are there to make sure that the intricate system of neurons, like the complex circuitry of a telephone exchange, form and maintain correct connections.

It is fair to say that Nogo is not the first molecule discovered that inhibits in this way. In fact, Steve Moore was quick to point out that "Nogo is but one of a number of inhibitory molecules", and any treatments encouraging the regeneration of damaged nerves will have to deal with most of them. However, he also adds that it's "a major one and of considerable importance" and that it "rates alongside the other major inhibitory factor, myelin associated glycoprotein" - or MAG for short.

The race is now on to find the Nogo receptor, the protein attached to nerve cells with which the Nogo molecule binds to and transmits its inhibitory message. "This will be the area where possible therapeutic intervention arises," said Moore. It is conceivable that by blocking this receptor or stopping Nogo from reaching this target, its inhibitory effect could be broken down.

Researchers are still a long way off winning the war against brain and spinal injury, and the Nogo discovery is just another battle won in the fight to gain full recovery of nerve function after injury. Nevertheless, it is a step in the right direction, both for opening up new lines of medical research in this area and providing new hope for those paralysed.