Keep those synapses firing: Could this be the key to understanding the origin of brain diseases?

One of the key findings in Alzheimer’s disease is a loss of synaptic connections. The synapse is the place where brain cells communicate with each other via their dendritic branches. The cells do not actually touch but are separated by a space called the synaptic cleft. It is across this space that brain chemicals or neurotransmitters cross to stimulate the adjoining brain cells and trigger further electrical messages to be passed along forming neural circuits or pathways.

Without synapses brain cells are unable to communicate to each other.

Sorry, I'm going to get a bit technical here, but it’s important to help understand the article. Sets of particular proteins that bind together to form a molecular hub called the postsynaptic density or PSD occur at the synapse, in the terminals of the dendrites. Animal studies had previously shown that the PSD plays an important role in brain disease and behaviour. However until now, little has been known about the human PSD.

Researchers from the Welcome Trust Sanger Institute and Edinburgh University have used a technique called proteomics to extract PSD’s from the synapses of patients undergoing brain surgery. Their findings are quite remarkable.

They have discovered a total of 1461 proteins, each encoded by a different gene in these human synapses. This then allowed them to systematically identify those diseases that affect the human synapse.

Professor Grant who led the research team revealed that over 130 brain diseases involve the PSD including Alzheimer’s, Parkinson’s, some forms of autism and learning disability.

Professor Noebels, Professor of Neurology, Neuroscience and Human Genetics at Baylor College of medicine said that of the 1461 proteins identified, “every seventh protein is involved in a known clinical disorder and half of them are repeat offenders. Researchers will now have a strategic starting point to start to unravel the complexity of brain disorders”

The research group has also created a first molecular network to show just how many of the proteins and diseases are interconnected.

As a sign of tremendous collaboration and desire to accelerate further discovery and use of this data, the scientists have released all of their findings into a public domain at their website G2Cdb No wikileaks required here. It’s all there to be shared.

They suggest that the proteome of the PSD will help us to gain further understanding of the brain in the same way that the genome assisted our understanding of DNA.

Other fascinating findings Include:

• That the proteins in PSD are important for certain cognitive behaviours such as learning, memory, emotion and mood

• And also for social behaviours, addiction and drug abuse.

Looking at how the PSD has evolved over time and contrary to expectations, the researchers discovered that the PSD has been resistant to change over the millennia. This means that synapses of rodents are not that dissimilar from humans, making further research using rat and mice models very suitable for studying human brain disease. Looks like we have more in common with our rodent friends than previously recognised.

These findings provide further valuable clues adding to our understanding of the brain and how some brain diseases may develop.

Àlex Bayés, Louie N van de Lagemaat, Mark O Collins, Mike D R Croning, Ian R Whittle, Jyoti S Choudhary, Seth G N Grant. Characterisation of the proteome, diseases and evolution of the human postsynaptic density. Nature Neuroscience, December 19, 2010 DOI: 10.1038/nn.2719