Broken brain protein key to treating MND

A BROKEN protein recycling system in the brain and spinal cord may underlie all forms of motor neurone disease (MND), scientists have learned.

The discovery could pave the way to new treatments for the devastating disorder, whose victims include top physicist Professor Stephen Hawking.

MND, also known as amytrophic lateral sclerosis (ALS), causes muscles to weaken and waste away, leading to crippling paralysis.

The ability to swallow and breathe is affected, commonly resulting in death within three years.

Around 5,000 people in the UK suffer from MND and although the disease can run in families, the exact cause of it has so far remained a mystery.

Today, however, scientists in America said they had uncovered the biological key to the condition.

It is a protein called ubiquilin 2 which plays a crucial role in recycling damaged or misshapen proteins in motor nerves.

Proper functioning of neurons depends on efficient recycling of proteins in the cells.

When this system breaks down, the nerve cells cannot repair or maintain themselves and become severely damaged.

Lead researcher Professor Teepu Siddique, from Northwestern University in Chicago, said: “This opens up a whole new field for finding an effective treatment for ALS.

“We can now test for drugs that would regulate this protein pathway or optimise it, so it functions as it should in a normal state.”

Protein recycling may also be involved in other neurodegenerative diseases, including Parkinson’s and Alzheimer’s, say the researchers writing in an early online edition of the journal Nature.

All are characterised by aggregations of abnormal proteins.

Ubiquilin 2 belongs to the ubiquitin family of proteins that are widespread throughout the body.

Ubiquitins are vital to protein recycling, labelling damaged proteins as “rejects” and marshalling them to a recycling centre in the cell called the proteosome.

There, the defective molecules are broken down into constituent amino acids which can then be used to build new proteins.

The scientists discovered that ubiquilin 2 was not functioning properly in people with MND.

Instead of taking damaged proteins to be recycled, it allowed them to accumulate in the motor neurons of the spinal cord and specific regions of the brain.

The protein accumulations, resembling twisted lengths of yarn, caused the damage to neurons.

Co-author Dr Han-Xiang Deng, also from Northwestern University, said: “This study provides robust evidence showing a defect in the protein degradation pathway causes neurodegenerative disease.

“Abnormality in protein degradation has been suspected, but there was little direct evidence before this study.”

Dr Belinda Cupid, head of research at the Motor Neurone Disease Association, said: “This is a big news story for motor neurone disease research.

“The discovery of mutations in the UBQLN2 gene in families with the rare, inherited form of motor neurone disease has unlocked the significance of this damaged protein in all forms of the disease.

“We’ve known for some time that the waste and recycling system in motor neurones is damaged, but this is the first time that there has been direct proof.

“This discovery provides researchers with an exciting new avenue to explore as they search for an effective treatment.”