Pharmacological studies using iPSC-derived neurons from patients with schizophrenia

Abstract

Schizophrenia is characterized by positive symptoms, negative symptoms and cognitive dysfunction. Although the abnormal neuronal development, impaired synaptic functions and impaired neural circuit functions are suggested to be the causes of psychiatric disorders, the molecular and cellular etiology of schizophrenia remains largely unclear. iPS-related technologies can be powerful for not only understanding the molecular and cellular etiology of schizophrenia but also drug discovery research. In 2011, the first iPS cells derived from patients with schizophrenia harboring a DISC1 mutation were generated. Subsequently, many iPS cells from patients with schizophrenia were established for understanding the molecular and cellular disease phenotypes of the differentiated neuronal cells. For replicating disease phenotypes with iPSC-derived neuronal cells, it is important to develop the differentiation strategies for generating cell-type specific cultures of various types of neurons, astrocytes and oligodendrocytes. Especially, scalable cultures of iPSC-derived neuronal cells are valuable platforms for drug discovery research. In this review, the focus has been made on the iPSC differentiation technology, pharmacological and drug discovery studies with iPSC-derived neurons from patients with schizophrenia. Continued advancement of the iPSC-related technologies and research will help the success in central nervous system drug discovery and development.