Incorrectly Cleaved Protein Leads To Schizophrenia

Main Category: Schizophrenia
Also Included In: Psychology / Psychiatry;  Mental Health
Article Date: 15 Jul 2008 - 2:00 PDT

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Schizophrenia is a disease that strikes an average of 4000 Belgians every year. The causes of this psychiatric disorder are not yet clear. But now, VIB researchers connected to the Katholieke Universiteit Leuven have discovered that a disturbed cleavage of the Nrg-1 protein lies at the basis of the development of the disease. Greater understanding of this molecular process is a first step toward improved diagnosis and more effective treatment of schizophrenia and other related disorders.

What is schizophrenia?

Schizophrenia is a mental disorder that appears in about 1 out of every 250 Belgians, manifesting most often between the ages of 15 and 30. This disease of the brain seriously disturbs the person's thinking, emotional life, and behavior. The disease is characterized by episodes of psychotic symptoms: abnormal ideas and changes in perception, behavior and thinking occur, through which it is difficult to understand how the person feels. Typical symptoms of the disorder are: delusions, hallucinations, chaotic behavior, etc.

The origin of the disease..

Up to now, no clear cause of schizophrenia has been found, although hereditary factors certainly play a role in the development of the disease. In addition, living and working conditions determine the disorder's progress. Research into schizophrenia has also shown that there is a disturbance of the activity of the frontal and temporal areas in the brain, which is connected with a disturbed equilibrium among the substances (proteins) that are needed for neuronal functioning. Schizophrenia is treated using anti-psychotic and neuroleptic medicines.

Research leads to new insights into the molecular causes

The molecular story hidden behind schizophrenia is still not at all clear. However, previous scientific studies have indeed shown that a disturbed functioning of the Nrg-1 protein is linked to the development of the disease. Now, the recent research results obtained by Tim Dejaegere and his colleagues connected to VIB and K.U.Leuven reveal how the functioning of Nrg-1 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 cleaved in the right way. This cleavage is the responsibility of a molecular 'scissors' called Aph1B/C-gamma-secretase. When this scissors is absent, Nrg-1 is not cleaved, which leads to behavioral disturbances in laboratory animals that bear a striking similarity to some of the symptoms of schizophrenia. This syndrome can be corrected by administering anti-psychotic medicines. Additional studies have also shown that a genetic alteration near the site of Nrg-1 cleavage, which was detected in schizophrenia patients and which increases the risk of this disease, results in incorrect cleavage of Nrg-1 by the gamma-secretase.

The researchers are suggesting that a disturbed cleavage of Nrg-1 plays a crucial role in the development of schizophrenia and other related psychiatric disorders. This discovery is a new step forward in the quest for improved diagnosis and targeted treatment of the disease.

Relevant scientific publication

Dejaegere et al., Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment, PNAS, 2008. The online publication will be available via PNAS Early Edition (http://www.pnas.org/content/early/recent) after the expiration of the embargo (Monday, 14 July 2008, at 11:00 pm Belgium Time).

Funding

This research has been funded by VIB, K.U.Leuven, FWO, IUAP, a Methusalem grant from the Flemish
Government and European Union Grant MEMOSAD.

VIB, the Flanders Institute for Biotechnology, is a non-profit research institute in the life sciences. Some 1100 scientists and technicians conduct strategic basic research on the molecular mechanisms that control the functioning of the human body, plants, and micro-organisms. Through a close partnership with four Flemish universities - Ghent University, the Katholieke Universiteit Leuven, the University of Antwerp, and the Vrije Universiteit Brussel - and a solid investment program, VIB unites the forces of 65 research groups in a single institute. Their research aims at fundamentally extending the frontiers of our knowledge. Through its technology transfer activities, VIB strives to convert the research results into products for the benefit of consumers and patients. VIB also develops and distributes a broad range of scientifically substantiated information about all aspects of biotechnology.

VIB, the Flanders Institute for Biotechnology