Genetic abnormalities of a stress response gene promote neurodevelopmental diseases

초록

We identified a gene that expresses a protein responsible for a vital role in cellular stress responses and the regulation of protein synthesis, including the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. Genetic alterations of the gene have been associated with neurodegenerative diseases, including Alzheimer's disease and microcephaly, where ER stress and UPR dysregulation have been detected. Previous studies have shown that different mutated forms of the gene have been detected in various human diseases, such as infantile cirrhosis, growth impairment, and neurodevelopmental diseases, including microcephaly. However, the specific functional defects associated with each mutated form contributing to neurodevelopmental diseases remain poorly understood. In this study, we employed molecular and biochemical methodologies to investigate the molecular mechanisms of the mutation form in human cells, particularly in neurons derived from induced pluripotent stem cells (iPSCs). Our results suggest a potential mechanism by which the dysfunctional form of the gene may impact molecular pathways associated with cellular stress responses. Further studies using iPSC-derived neurons will reveal the critical functions of the gene in neurodevelopment.