Schizophrenia has been linked to a split protein, opening a path to a new class of treatments for the common mental illness.

It was once thought - wrongly - that sufferers have a "split personality" but now, researchers at the Flanders Institute for Biotechnology, VIB, and University of Leuven have discovered that faulty snipping of a protein called neuregulin, or Nrg-1, lies at the basis of the development of the disease.

Greater understanding of this molecular process is a first step toward improved diagnosis of the one in 100 people who suffer from the delusions, hallucinations and disturbed thinking and more effective treatment of schizophrenia and other related disorders.

Up to now, no clear cause of schizophrenia has been found, although hereditary factors certainly play a role along with living and working conditions, with the condition being more common in urban dwellers and younger people.

However, previous scientific studies have suggested that faulty functioning of the Nrg-1 protein plays a role.

Today, in the Proceedings of the National Academy of Sciences, researchers at the Flanders Institute for Biotechnology, VIB, and Catholic University of Leuven report that they have discovered that faulty cleavage of the Nrg-1 protein lies at the basis of the development of the disease.

The results obtained by Tim Dejaegere and his colleagues connected to VIB and the university reveal how the process of snipping Nrg-1 to the right length becomes disturbed.

The Nrg-1 protein - an essential factor in the development and proper functioning of our nervous system and, consequently, in the functioning of our brain - can carry out its function properly only after it has been cut in the right way by a pair of molecular 'scissors' called Aph1B/C-gamma-secretase.

Without these scissors, Nrg-1 is not cleaved, which leads to behavioural disturbances in laboratory animals that bear a striking similarity to some of the symptoms of schizophrenia.

And the animals respond to conventional treatments - antipsychotic or neuroleptic drugs, haloperidol and clozapine - for the mental disorder.

Additional studies have also shown that a mutation linked with the disease that alters part of the Nrg-1 near where it is cut, results in incorrect cleavage of Nrg-1.

Existing drugs used to treat schizophrenia all work by influencing a brain messenger chemical, dopamine, and date back to the 1950s. But faulty signalling is thought to result from a more basic cause.

One approach would be to develop drugs that act like the molecular scissors and see if they can treat schizophrenia symptoms. "If so, you would indeed have a radically new class of antipsychotic drugs," said Dr Dejkaegere.

"As this is fundamental research, there are no immediate implications for diagnosis and treatment, but our results strengthen the case for an involvement of abnormal neuregulin signalling in schizophrenia and are bound to increase the interest in the clinical testing of drugs that modulate neuregulin signalling," commented Dr Dejkaegere with Dr Bart De Strooper.

At long last, a more unified picture of what is going on is emerging. "After years of groping in the dark and following an huge number of potential leads, research interest is now focusing on a few key molecular players, of which neuregulin is the most prominent."