Clue to cause of nerve diseases

Brain cell death can cause disease

Scientists have uncovered a new factor influencing neurodegenerative disorders such as motor neurone disease and Huntington's disease.

These diseases are associated with protein clumps in nerve cells.

The latest study showed how the cells' waste disposal process, which prevents clump formation, is dependent on transporter proteins called dyneins.

The study, led by the Cambridge Institute for Medical Research, is published in Nature Genetics.

These findings provide us with real insight into the molecular basis of certain motor neuron diseases Dr David Rubinsztein

The researchers, who collaborated with a team from the Medical Research Council, hope their work could lead to new treatments.

Late-onset neurodegenerative diseases are a major health burden on the population.

Little is known about the chemical changes that trigger the degeneration of nerve cells.

But it is clear that the process is, in some cases, associated with the accumulation of clumps of toxic proteins within the cells.

Cellular transport

The researchers focused on dyneins, as they were already known to be involved in moving proteins around inside nerve cells.

They found that dyneins play a crucial role in transporting toxic proteins to the waste disposal units of cells.

And by using chemical and genetic modification to block dynein activity, they showed that when dyneins were either defective or absent, the waste disposal system stalls, allowing toxic proteins to build up to potentially damaging levels.

Next they crossed flies with a form of Huntington's disease with flies with reduced dynein activity.

The offspring had a much worse form of Huntington's - suggesting a failure of the dynein system accelerates the development of the disease.

Similar experiments in mice appeared to confirm the finding.

Analysis of cells taken from animals with compromised dynein systems showed signs of reduced activity of the waste disposal process, called autophagy.

The researchers hope their work could stimulate the development of treatments to reduce the levels of toxic proteins in nerve cells.

This, they believe, might eventually help delay the onset of disease, and perhaps even reverse symptoms.

Lead researcher Dr David Rubinsztein, of the Cambridge Institute for Medical Research, said: "These findings provide us with real insight into the molecular basis of certain motor neuron diseases and the mechanisms by which toxic proteins accumulate and are broken down.

"They also may help development of possible therapeutic strategies for these diseases."

Dr Brian Dickie, director of research development at the Motor Neurone Disease Association, said: "The malfunction of cellular transport processors is an emerging area of interest in Motor Neurone Disease and other neurological disorders.

"This work is likely to open up significant new avenues of investigation, which will be key to developing much-needed effective treatments for Motor Neurone Disease."