Modeling human neurodegenerative diseases

Human patient-specific neurons will be crucial for understanding adult-onset neurodegenerative diseases. Induced pluripotent stem cells (iPSCs) derived from human skin fibroblasts and their differentiation into subtype-specific neurons are emerging as a cellular model for investigating these diseases. However, iPSCs and the differentiated neurons are reset to an embryonic stage during reprogramming. These embryonic or young neurons are inappropriate for modeling adult-onset neurological diseases. We have established a direct reprogramming approach by converting adult human skin fibroblasts to highly pure subtype-specific neurons without passing a stem cell stage. These neurons maintain aging features of their parental fibroblasts and are therefore ideal for modeling adult-onset neurodegeneration. Using this unique cell model, research efforts are on understanding disease mechanism, therapeutic drug identification and validation.