| 1 | J. Neurochem. 2012 May 121: 561-74 |
|---|---|
| PMID | 22191421 |
| Title | The serine protease inhibitor neuroserpin regulates the growth and maturation of hippocampal neurons through a non-inhibitory mechanism. |
| Abstract | Neuroserpin is a brain-specific serine protease inhibitor that is expressed in the developing and adult nervous system. Its expression profile led to suggestions that it played roles in neuronal growth and connectivity. In this study, we provide direct evidence to support a role for neuroserpin in axon and dendritic growth. We report that axon growth is enhanced while axon and dendrite diameter are reduced following neuroserpin treatment of hippocampal neurons. More complex effects are seen on dendritic growth and branching with neuroserpin-stimulating dendritic growth and branching in young neurons but switching to an inhibitory response in older neurons. The protease inhibitory activity of neuroserpin is not required to activate changes in neuronal morphology and a proportion of responses are modulated by an antagonist to the LRP1 receptor. Collectively, these findings support a key role for neuroserpin as a regulator of neuronal development through a non-inhibitory mechanism and suggest a basis for neuroserpin's effects on complex emotional behaviours and recent link to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Behav Brain Funct 2013 -1 9: 9 |
| PMID | 23425335 |
| Title | Investigation of rare variants in LRP1, KPNA1, ALS2CL and ZNF480 genes in schizophrenia patients reflects genetic heterogeneity of the disease. |
| Abstract | schizophrenia is a severe psychiatric disease characterized by a high heritability and a complex genetic architecture. Recent reports based on exome sequencing analyses have highlighted a significant increase of potentially deleterious de novo mutations in different genes in individuals with schizophrenia. This report presents the mutation screening results of four candidate genes for which such de novo mutations were previously reported (LRP1, KPNA1, ALS2CL and ZNF480). We have not identified any excess of rare variants in the additional SCZ cases we have screened. This supports the notion that de novo mutations in these four genes are extremely rare in schizophrenia and further highlights the high degree of genetic heterogeneity of this disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Sci Rep 2015 -1 5: 18209 |
| PMID | 26666178 |
| Title | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development. |
| Abstract | schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N?=?45) with schizophrenia and their unaffected parents (N?=?90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p?LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Sci Rep 2015 -1 5: 18209 |
| PMID | 26666178 |
| Title | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development. |
| Abstract | schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N?=?45) with schizophrenia and their unaffected parents (N?=?90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p?LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. |
| SCZ Keywords | schizophrenia, schizophrenic |