Incorrectly cleaved protein leads to schizophrenia

Jul 14, 2008

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.

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.

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.

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.

Source: VIB (the Flanders Institute for Biotechnology)

Explore further: Restrictions lifted at British bird flu farm

add to favorites email to friend print save as pdf

Related Stories

Novel Pathway Regulates Timing of Brain-Cell Development

Oct 05, 2006

Brain formation involves the carefully timed production of different types of nerve cells by neural stem cells: neurons are produced first, then astrocytes. Making too much of one kind of cell and too little of another at ...

Recommended for you

Restrictions lifted at British bird flu farm

13 hours ago

Britain on Sunday lifted all restrictions at a duck farm in northern England after last month's outbreak of H5N8 bird flu, the same strain seen in recent cases across Europe.

Recorded Ebola deaths top 7,000

Dec 20, 2014

The worst Ebola outbreak on record has now killed more than 7,000 people, with many of the latest deaths reported in Sierra Leone, the World Health Organization said as United Nations Secretary-General Ban ...

Liberia holds Senate vote amid Ebola fears (Update)

Dec 20, 2014

Health workers manned polling stations across Liberia on Saturday as voters cast their ballots in a twice-delayed Senate election that has been criticized for its potential to spread the deadly Ebola disease.

Evidence-based recs issued for systemic care in psoriasis

Dec 19, 2014

(HealthDay)—For appropriately selected patients with psoriasis, combining biologics with other systemic treatments, including phototherapy, oral medications, or other biologic, may result in greater efficacy ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.