Schizophrenia is a disease in which symptoms such as delusions, hallucinations, disorganized language and behavior appear, and can cause social dysfunction. Until now, a clear cause of schizophrenia has not been identified, and it is generally known as a disease caused by abnormalities in the brain. In the midst of this, a domestic research team has identified a correlation between cases of schizophrenia and the fetal neural development process.
The POSTECH research team (President Moo-Hwan Kim) conducted joint research with the Korea Brain Research Institute and the KAIST research team to find that MAD1 (Mitotic Arrest Deficient-1) protein, the causative factor of schizophrenia, can regulate the known function of bodies in nerve cells , said the day
Schizophrenia is one of the leading mental disorders causing astronomical social and medical costs. Therefore, as a global effort to understand the biological cause and the underlying treatment approach, a large-scale genome-wide association analysis (GWAS) study of schizophrenia was completed several years ago. From this, more than 100 genes associated with schizophrenia have been discovered, but more research is needed on how each gene may be associated with schizophrenia.
☞ Genome-wide association study (GWAS): A study that compares DNA markers by comparing the entire genome of people with a disease to the genome of people without the disease
MAD1L1 (Mitotic Arrest Defective-1 Like 1) gene has been shown to be highly associated with schizophrenia several times in several studies targeting GWAS and human schizophrenia patients. However, its function in the nervous system has not been directly known. Accordingly, the research team investigated the molecular mechanism of schizophrenia by investigating the role of MAD1, one of the products of the MAD1L1 gene, in key neurodevelopmental processes using mouse and human organoid (total cell) models.
The research team revealed that MAD1 is highly expressed during the development of the cerebral cortex, and that a lack of MAD1 causes problems in neuronal migration and neurite outgrowth.
In addition, it was confirmed that MAD1 is located in the intracellular Golgi apparatus and regulates the transport of vesicles from the Golgi apparatus to the cell membrane, which is important in determining the growth and polarity of migrating neurons. During this process, it was found that MAD1 physically interacts and cooperates with the protein KIFC3 (a member of the C3 kinesin family) to properly regulate the migration and differentiation of neurons by regulating the shape of the Golgi apparatus and nerve polarity.
As a result, it was identified that MAD1, which is the expression product of the gene associated with schizophrenia MAD1L1, is an important factor in the shape, polarity and mobility of neurons by regulating the functionality of the Golgi apparatus in neurons. This provides new evidence that supports the old theory that what causes schizophrenia is abnormal neurogenesis in the fetal stage.
Professor Park Sang-ki from the Department of Life Sciences, POSTECH, who led the study, said, “The results of this study show that MAD1 is a critical regulator of neurodevelopment and that functional abnormalities in MAD1 may provide a new basis for for understanding. causes of schizophrenia in the period of neurogenesis.” .
Meanwhile, this research was carried out with the support of the mid-level researcher support project, the new drug field source technology development project, the new researcher support project, the leading research center support project, the brain research institute’s own project, and the academic next generation support project. The results of the research were published in the international journal Molecular Psychiatry.
[참고자료]
Schizophrenia-associated Mitotic Arrest Deficient-1 (MAD1) regulates the polarity of migrating neurons in the developing neocortex : https://www.nature.com/articles/s41380-022-01856-5
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