Set of proteins linked to over 130 brain diseases discovered

WASHINGTON - Scientists at the Wellcome Trust Sanger Institute and Edinburgh University have studied human brain samples to isolate a set of proteins that account for over 130 brain diseases.

The brain is the most complex organ in the body with millions of nerve cells connected by billions of synapses. Within each synapse is a set of proteins, which, like the components of an engine, bind together to build a molecular machine called the postsynaptic density - also known as the PSD.

Professor Seth Grant and his team have extracted the PSDs from synapses of patients undergoing brain surgery and discovered their molecular components using a method known as proteomics. They found 1461 proteins, each one encoded by a different gene, are found in human synapses.

“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,” said Grant.

“Rather than ’rounding up the usual suspects’, we now have a comprehensive molecular playlist of 1000 suspects. Every seventh protein in this line-up is involved in a known clinical disorder, and over half of them are repeat offenders. Mining the postsynaptic proteome now gives researchers a strategic entry point, and the rest of us a front row seat to witness neuroscience unravel the complexity of human brain disorders,” said Professor Jeffrey L Noebels, Professor of Neurology, Neuroscience and Human Genetics at Baylor College of Medicine.

The findings open several new paths toward fighting these diseases.

“Since many different diseases involve the same set of proteins we might be able to develop new treatments that could be used on many diseases. We also can see ways to develop new genetic diagnostic tests and ways to help doctors classify the brain diseases,” said Grant.

To accelerate discovery and application of their data, the scientists have released all their data into the public domain on their website - G2Cdb. The team suggests that the data on the proteome of the PSD will be extremely useful for understanding the brain in the same way the genome was useful for understanding DNA.

The team found that proteins in the PSD are especially important for cognitive behaviours such as learning and memory, emotion and mood, as well as social behaviours and addiction or drug abuse. The findings provide deep insights into how a DNA mutation can impact on fundamental aspects of our behaviour.

They also found that the PSD proteins changed much more slowly than expected, revealing that the PSD has been highly conserved or constrained from changing during evolution.

“This splendid collaborative study is a major step forward which will surely illuminate the causes of many of the major mental health and neurological disorders that are so common in Britain as well as indicating new ways to develop treatments for these most disabling diseases,” concluded Jonathan R Seckl, of the Queen’s Medical Research Institute, Edinburgh. (ANI)