Since the Neuregulin 1 protein plays a key role in brain development and is more abundant in fetal brains, DNA changes that alter the expression of this protein may contribute to schizophrenia by modifying the development and wiring of the brain, Law says. By understanding how this novel protein works in the brain, we may be able to target it in people with the disease.
The researchers showed that the genetic change that causes overproduction of Neuregulin 1 type 4 is part of a DNA sequence called a promoter, which enables genes to be coded for proteins. A protein called a transcription factor binds to the promoter and helps other proteins to express the gene. When the promoter is altered, the transcription factor may not bind properly and impair genetic expression. Law and colleagues showed that alteration of the promoter in the genetic sequence linked to schizophrenia resulted in altered amounts of Neuregulin 1 type 4.
For the first time, we have identified a promoter for the Neuregulin 1 gene and showed that the activity of that gene is altered by a single genetic variation in this promoter, Law says. These results will probably help us understand how DNA variations affect the function of this gene and lead to symptoms of schizophrenia.
The researchers are now planning to investigate further the role of Neuregulin 1 type 4 in brain development and behavior and determine how various alterations of the Neuregulin 1 gene lead to schizophrenia.
By better understanding the genetic causes of schizophrenia, we can start to make sense of the underlying biology of the disease and develop improved therapies based on peoples genes, Law says. The insight gained on the Neuregulin 1 gene is, I hope, bringing us c
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Contact: Pat Pages
ppages@asbmb.org
301-634-7366
American Society for Biochemistry and Molecular Biology
9-Aug-2007