New clue to the causes of neurodegenerative diseases

Scientists funded by the Medical Research Council (MRC), the Wellcome Trust, BBSRC - the Biotechnology and Biological Sciences Research Council and the EU have made an important discovery about the mechanisms underlying degenerative brain diseases.

The findings, published in this week's edition of the science journal Nature Genetics, may have implications for therapeutic strategies for some forms of motor neuron disease, Huntington's disease and Alzheimer's.

Late-onset neurodegenerative diseases are a major health burden on the population, yet little is known about the chemical changes that trigger the degeneration of nerve cells. However, many of these diseases are characterised by accumulation, inside nerve cells, of clumps of toxic proteins. The new research - carried out at the Cambridge Institute for Medical Research, the MRC Mammalian Genetics Unit at Harwell and the Department of Genetics, University of Cambridge - has concentrated on tiny molecular motors called dyneins, which are known to be important for moving proteins around inside nerve cells. The researchers found that dyneins play a crucial role in the delivery of toxic proteins to the waste disposal units of cells. When dyneins are defective or absent, this waste disposal system is stalled, clumps of proteins appear, and cell function is compromised.

The study found that failure of the dynein system causes the degeneration in a form of motor neuron disease, and that it is also involved in other conditions such as Huntington's disease. It also provided further evidence for the idea, pioneered by the same group of scientists, that a key factor in the severity of these diseases is the rate at which these toxic clumps of protein can be removed. Enhancing the degradation of these protein clumps has the potential to delay the onset of, or even reverse, this group of diseases. This might be exploited in new approaches to prevention or therapy.

The lead scientist, 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 contribute greatly to our understanding of possible therapeutic strategies for these diseases."