A Mutation in NPAS3 That Segregates with Schizophrenia in a Small Family Leads to Protein Aggregation

In this study, we demonstrate that NPAS3 is prone to aggregation, and that the V304I mutation in NPAS3 increases this propensity in both bacterial and mammalian expression systems. We also show that NPAS3-V304I reduces soluble endogenous NPAS3, and increases insoluble endogenous NPAS3 and leads to alteration of transcriptional activity. These results suggest that protein aggregation, potentially leading to cell dysfunction via a loss of protein function through sequestration, may contribute to the pathogenesis of schizophrenia and other forms of mental illness. Further exploration of the mechanisms leading to abnormal protein quality control could lead to new therapeutic targets. < br / > Mol Neuropsychiatry 2016;2:133-144
Source: Molecular Neuropsychiatry - Category: Neuroscience Source Type: research