Navigation Links
The genetic basis of brain diseases
Date:12/19/2010

In research published today, scientists have studied human brain samples to isolate a set of proteins that accounts for over 130 brain diseases. The paper also shows an intriguing link between diseases and the evolution of the human brain.

Brain diseases are the leading cause of medical disability in the developed world according to the World Health Organisation and the economic costs in the USA exceeds $300 billion.

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. Although studies of animal synapses have indicated that the PSD could be important in human diseases and behaviour, surprisingly little was known about it in humans.

A team of scientists, led by Professor Seth Grant at the Wellcome Trust Sanger Institute and Edinburgh University, have extracted the PSDs from synapses of patients undergoing brain surgery and discovered their molecular components using a method known as proteomics. This revealed that 1461 proteins, each one encoded by a different gene, are found in human synapses. This has made it possible, for the first time, to systematically identify the diseases that affect human synapses and provides a new way to study the evolution of the brain and behaviour.

"We found that over 130 brain diseases involve the PSD far more than expected," says Professor Grant. "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," says Professor Grant.

"Rather than 'rounding up the usual suspects', we now have a comprehensive molecular playlist of 1000 suspects," says Professor Jeffrey L Noebels, Professor of Neurology, Neuroscience and Human Genetics at Baylor College of Medicine. "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."

The findings open several new paths toward tackling 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", says Professor Grant. To aid in this objective the group has created the first molecular network, a roadmap of the molecular organisation of human synapses, which shows how the many proteins and diseases are interconnected. "We also can see ways to develop new genetic diagnostic tests and ways to help doctors classify the brain diseases".

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 scientists were able to use their study of diseases to identify the biological roots of human behaviour. They 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.

The team examined the rate of evolution of the PSD proteins over millions of years of mammalian evolution, expecting the proteins to evolve at the same rate as other proteins. In a fascinating and unexpected twist to the story, the team 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.

"The conservation 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," said Professor Grant. "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."

Professor Jonathan R Seckl, Moncrieff-Arnott Professor of Molecular Medicine and Executive Dean, College of Medicine and Veterinary Medicine, The Queen's Medical Research Institute, Edinburgh, says: "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."

This project was conducted as part of the Genes to Cognition Program, which is a research program aimed at understanding the molecular basis of behaviour and brain disease.


'/>"/>

Contact: Don Powell
press.officer@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

Related biology news :

1. 23andMe receives NIH funding to evaluate web-based research on the genetics of drug response
2. New research shows dolphin by-catch includes genetic relatives
3. Genetic variants linked to increased risk of common gynecological disease
4. Genetic studies of human evolution win researcher 2011 Gani Medal
5. New UCLA study raises questions about genetic testing of newborns
6. New study suggests that a propensity for 1-night stands, uncommitted sex could be genetic
7. Blast from the past: Jack pine genetics support a coastal glacial refugium
8. Forget Farmville, heres a game that drives genetic research
9. Transcription factor scan identifies genetic cause for inherited blindness
10. Researchers learn that genetics determine winter vitamin D status
11. Researchers discover potential genetic target for heart disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/20/2016)... DALLAS , June 20, 2016 ... criminal justice technology solutions for public safety, investigation, ... by the prisons involved, it has secured the ... Corrections (DOC) facilities for Managed Access Systems (MAS) ... (4) additional facilities to be installed by October, ...
(Date:6/7/2016)... 2016  Syngrafii Inc. and San Antonio Credit ... includes integrating Syngrafii,s patented LongPen™ eSignature "Wet" solution ... will result in greater convenience for SACU members ... maintaining existing document workflow and compliance requirements. ... Highlights: ...
(Date:6/1/2016)... , June 1, 2016 ... in Election Administration and Criminal Identification to Boost Global ... a recently released TechSci Research report, " Global Biometrics ... Region, Competition Forecast and Opportunities, 2011 - 2021", the ... billion by 2021, on account of growing security concerns ...
Breaking Biology News(10 mins):
(Date:12/2/2016)... ... 02, 2016 , ... Robots will storm the Prudential Center in Boston, MA ... event, which is held on the United Nations International Day of Persons with Disabilities, ... the workplace. Suitable Technologies is partnering with NTI to showcase how technology can help ...
(Date:12/2/2016)... world leader in rapid infectious disease tests, introduced the Company,s newest product, the INSTI ... (Photo: http://photos.prnewswire.com/prnh/20161201/444905 ) Continue Reading ... ... , bioLytical was invited by the Clinton ... HIV Self Test to 350 pharmacy representatives in Nairobi and ...
(Date:11/30/2016)... , November 30, 2016 The global ... few players hold a dominant share in the overall ... Laboratories International, Inc., and Merck KGaA, held a lion,s ... Transparency Market Research observes that these companies are expected ... development products that are do not require rabbit pyrogen ...
(Date:11/30/2016)... , Nov. 30, 2016  The Allen Institute ... Collection: the first publicly available collection of gene ... that target key cellular structures with unprecedented clarity. ... these powerful tools are a crucial first step ... better understand what makes human cells healthy and ...
Breaking Biology Technology: