Link between 130 brain diseases is pinpointed by Scottish scientists

Published on Sunday 19 December 2010 17:07

SCOTTISH scientists have helped identify proteins that are "centre stage" for about 130 brain diseases.

The discovery could lead to new treatments for disorders such as Alzheimer's and autism, including multifunctional drugs that can treat more than one condition.

A team of British and American scientists isolated the group of proteins after investigating synapses, connection points in the brain's system of neurons, in patients undergoing brain surgery.

In total 1,461 proteins, each encoded by a different gene, were found to be active in human synapses. The proteins work together to form a molecular machine known as the postsynaptic density, or PSD.

Professor Jonathan Seckl, from the Queen's Medical Research Institute in Edinburgh, said: "This splendid collaborative study is a major step forward which will surely illuminate the causes of many of the major mental health and neuro- logical disorders that are so common in Britain as well as indicating new ways to develop treatments for these most disabling diseases."

Professor Seth Grant, from the Wellcome Trust Sanger Institute in Hinxton, Cambridgeshire, said: "We found that over 130 brain diseases involve the PSD - far more than expected.

"These diseases include common debilitating diseases such as Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders, as well as epilepsies and childhood developmental diseases including forms of autism and learning disability.

"Our findings have shown that the human PSD is at centre stage of a large range of human diseases affecting many millions of people."

One in seven "suspect" in the protein line-up is involved in a known clinical disorder, said the scientists, whose research is reported in the journal Nature Neuroscience. "Over half of them are repeat offenders," said co-author Professor Jeffrey Noebels, from the Baylor College of Medicine in Houston, Texas.

Since many diseases involve the same proteins, the scientists believe the research could lead to multi-condition treatments.

As a first step, they have created a molecular "road map" showing how the many proteins and disorders are connected.

"We also can see ways to develop new genetic diagnostic tests and ways to help doctors classify the brain diseases," said Prof Grant.

All the "proteome" data have been posted on the internet to help other researchers.

One important finding was that PSD proteins play key roles in learning, memory, emotion and mood, as well as social behaviours and addiction.

Another discovery was that synaptic proteins appear to have evolved at a slower rate than other proteins.

The proteins had been highly conserved across different evolving species.

Prof Grant said: "The con- servation of the structure of these proteins suggests that the behaviours governed by the PSD and the diseases associated with them have not changed much over many millions of years.

"It also shows that synapses in rodents are much more similar to humans than we expected, showing that mice and rats are suitable models for studying human brain disease."