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Last updated on April 19, 2014 at 5:20 EDT

Researchers Discover Important Clue To Motor Neuron Disease

November 18, 2008

Scientists say the identification of a specific molecule could be key to understanding the cause of motor neuron disease (MND) and other neurodegenerative disorders.

The study of the molecule, Wnt3, raises the hope of new treatments being developed.

The London-based researchers said the molecule plays a key role in establishing connections between nerve cells and the muscles they control and that these connections become progressively weaker in MND patients.

Without properly-formed connections – or synapses – the muscle cannot receive the nerve signal that tells it to contract, resulting in the muscle weakness that is typical of MND.

But scientists say it is still unclear how synapses are formed in normal circumstances and this has made it very difficult to pin down what goes wrong in MND.

The researchers, from University College London and King’s College London, identified Wnt3 as key to the process.

Wnt3 assists a second molecule, called Agrin, which co-ordinates construction of the connection – or synapse.

“The work we are publishing today puts an important piece of the puzzle in place and offers up a new possibility for developing drugs to treat MND and other neurodegenerative diseases,” said lead researcher Professor Patricia Salinas.

“If we can build up a thorough picture to show how synapses are normally formed between nerves and muscles we can start to look for any elements that aren’t working properly in people with MND.

“This might also lead to strategies for nerve repair after an injury.”

The researchers looked at the function of Wnt signals in chickens, mice and in cells and in all three cases, it was shown to enhance the effectiveness of Agrin.

“Chickens that don’t have the Wnt signal in their developing wings have all of the muscle tissue that we would expect to see, but they don’t make strong connections between nerves and muscles,” said Salinas.

“So we know that Wnt is definitely affecting synapse formation rather than anything else to do with muscles.

Salinas said now that they understand the role Wnt plays they can begin to explore any role it plays in MND and whether it could be a good target for treating this type of neurodegenerative disease.

“We know from recent research that signs of motor neuron damage, on a cellular level, in models of MND occur very much earlier than the symptoms appear, so any new knowledge of how healthy motor neurons and muscles interact will give us new clues about what might be going wrong in those people affected by this cruel disease,” said Dr Belinda Cupid, of the MND Association.

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