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Headlines*: May 2006

* Newsletter of NISAD (Neuroscience Institute of Schizophrenia and Allied Disorders)

Why Proteomics is the New Buzzword in Worldwide Schizophrenia Research

The old idea that each of the human body's 30,000 genes produces a single protein which plays a role in biological construction has been discarded. Current evidence shows that throughout life, when molecules are required, genes are transcribed first to the corresponding messenger ribonucleic acids (mRNAs), then translated to their protein counter­parts - and that this process of transcrip­tion and translation is continually subject to modifications arising from genetic predispositions and environmental interactions. Thus it is now estimated that if the human genome contains 30,000 expressed genes, there may be the potential to express as many as one million different proteins - the building blocks of the body and brain.

The prospect of identifying what is now termed an individual's 'proteome' is daunting. Fortunately, the birth of 'proteomics', an umbrella term encom­passing the many tools available to investi­gate proteins expressed within cells, fluids, tissues or organisms. has made this task more manageable. These proteomic methods have the power to display and quantify the functional expression of genes, enabling the measurement of disease-associated or phenotypic changes in proteins.

Schizophrenia, with its early develop­ mental and later degenerative/atrophic components, is a particularly complex disorder. We know that multiple, largely unidentified genetic and environmental risk factors interact to lead to disease and disease progression. However, the underlying functional changes at the cellular level remain unknown. This is where the strength of a proteomics approach lies, allowing researchers to identify, quantify and compare the levels of thousands of proteins in different brain areas.

42 protein differences detected in a schizophrenia 'hot spot'

The brain area known as the anterior cingulate cortex (ACC) plays a funda­mental role in cognition and attention, and has been a focus of neuroscience mental health research for some time. Its dysfunction has been directly linked to disorders such as obsessive-compulsive, bipolar and post traumatic stress, as well as to depression, autism and schizophrenia. All evidence identifies the ACC as a mental health 'hot spot' in the brain.

A NISAD-supported team at the University of Sydney has conducted the world's first proteomic analysis of the ACC in schizophrenia', using post mortem tissue from 10 schizophrenia patients and 10 normal controls. The results have identified 42 proteins in the Ace which are differently expressed in schizophrenia, some of which exhibit a 200 percent greater abundance than normal.

The University of Sydney team were able to link all but two of the proteins to specific genes, and has classified them as affecting the synapses, neuronal signaling and other functions. Eight of the altered proteins are involved in energy metabolism within the brain.

Some of the identified proteins have previously been linked to schizophrenia in earlier studies. Others shed new light on the origins of the disease, and present new pieces to fit into the complex puzzle being completed by such research.

* Clark D, Dedova I, Cordwell S, Matsumoto I. A proteome analysis of the anterior cingulate cortex grey matter in schizophrenia. Molecular Psychiatry 2006; 11: 459-470.