December 23, 2010
A Step Closer To Understanding Brain Diseases
(Ivanhoe Newswire) "“ By studying human brain samples, scientists have been able to isolate a set of proteins that account for over 130 different brain diseases "“ the leading causes of mental disability with an economic costs in the USA that exceeds $300 billion. This discovery provides new insight into the evolution of behavior.
The brain is a multifaceted organ in the body with millions of nerve cells connected by billions of synapses. It's rather complex if you didn't know already. Contained by each synapse is a set of proteins. These proteins "“ like the components of an engine "“ bind together to build a molecular machine called the postsynaptic density (PSD). Although prior studies of animal synapses have specified that the PSD may be vital in human diseases as well as behavior, surprisingly little was known about it in humans.
A team of scientists extracted the PSDs from synapses of patients undergoing brain surgery, and moreover discovered their molecular components via a method branded as proteomics. This revealed that 1461 proteins "“ each one encoded by a different gene "“ are found in human synapses. This has made it possible to analytically identify the diseases that have an effect on human synapses, in addition to providing a novel way to examine the evolution of the brain and behavior.
"We found that over 130 brain diseases involve the PSD "“ far more than expected," which Professor Seth Grant at the Wellcome Trust Sanger Institute and Edinburgh University, was quoted as saying. "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," adds Professor Grant.
"Rather than 'rounding up the usual suspects', we now have a comprehensive molecular playlist of 1000 suspects," which Professor Jeffrey L Noebels, Professor of Neurology, Neuroscience and Human Genetics at Baylor College of Medicine, was quoted as saying. "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 various novel paths toward tackling head-on 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", said Professor Grant. To aid in this objective the group has designed the foremost molecular network, a roadmap of the molecular organization of human synapses, which illustrates how the myriad 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."
The researchers were able to employ their study of diseases to identify the utter biological roots of human behavior. The authors add that proteins in the PSD are particularly essential for cognitive behaviors such as learning and memory, emotion and mood, in addition to social behaviors and addiction or drug abuse. These findings give deep insight into how a DNA mutation can impact the underlying aspects of our behavior.
In examining the rate of evolution of the PSD proteins over millions of years of mammalian evolution, researchers expected the proteins to evolve at an identical rate as other proteins. In an enthralling and moreover unforeseen twist to the story, it was also reported that the PSD proteins altered slower than expected, revealing that the PSD has been greatly conserved or constrained from shifting during evolution.
"The conservation of the structure of these proteins suggests that the behaviors 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."
"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," which 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, was quoted as saying.
SOURCE: Nature Neuroscience, December 22, 2010