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7 June 2010
A joint discovery by scientists in Scotland and Australia opens up a new molecular target for therapies for Alzheimers Disease and bipolar disorder.
The new target — a protein called dynamin — is already a major focus of research, with dynamin inhibitors currently undergoing early stage laboratory testing for their suitability as therapeutic drugs for epilepsy.
Researchers at the University of Edinburgh and Children’s Medical Research Institute (CMRI) in Sydney, led by Professor Mike Cousin in Edinburgh, found that a protein called GSK3 controls dynamin's functions in nerve terminals. Their work also revealed a surprising partnership between GSK3 and a previously discovered dynamin controller, cdk5.
GSK3 and cdk5 have previously been linked to bipolar disorder and Alzheimers disease. Professor Cousin discovered that the GSK3/cdk5 partnership exerts control over the rate of nerve cell communication in situations when the nerve cells are highly stimulated — which occurs in mood disorders and the early stages of Alzheimers.
A series of discoveries over the past 60 years, starting with the discovery by Australian psychiatrist and researcher John Cade that lithium is a useful treatment for bipolar disorder, has led to the realization that blocking the actions of GSK3 is an important strategy for the treatment of both bipolar disorder and Alzheimers Disease. But the reasons for this were unknown. “This discovery has helped put in place a key new piece of the puzzle” said Professor Phil Robinson of Children’s Medical Research Institute.
The Sydney team worked in collaboration with the Edinburgh group to reveal details of how these two proteins work together to control dynamin. “We have very sensitive mass spectrometers, which allowed us to discover that GSK3 acts a highly specific molecular switch for dynamin activity, but only after it has been given permission by cdk5 to do this,” said Professor Robinson.
“We haven’t found a treatment or a cure” said Professor Robinson of CMRI, “but we have found how one of the most important targets for the treatment of these conditions works, which opens up the possibility of designing much more effective treatments.”
“I’ve suspected for a long time that dynamin plays a key role in mood disorders, but this research has provided the first really clear evidence. We’ve already begun an extensive drug development program using dynamin inhibitors for treatment of epilepsy, so a lot of the information we get from those studies can hopefully be transferred to studies into targeting dynamin for the treatment of Alzheimers and bipolar disorder” said Professor Robinson.
The team’s findings were published today in Nature Neuroscience.
The work carried out by researchers at Children’s Medical Research Institute (CMRI) was partly funded by Jeans for Genes®, a major fundraiser of CMRI. You can support this work by wearing your jeans and buying a badge or making a donation on Jeans for Genes Day, Friday 6th August.
This story in the media
To hear Professor Robinson's interview with Fran Kelly on Radio National Breakfast, click here.
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