Abstract:

Neurological disorders are amongst the most widely studied human aliments. Yet, they are also one of the most poorly understood. An important role for genotype in the etiology of neurological disorders is suggested, even though most of these disorders are polygenic. For example, in schizophrenia and autism spectrum disorders, there is a 40–60 % concordance rate in monozygotic twins, with 60–90 % heritability. However, the mechanisms by which multiple genes and the genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are further compounded by the individual rarity of the genomic variations and their variable penetrance. Thus, conventional disease modeling that makes use of genome editing techniques to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders. With the advent of induced pluripotent stem cell (iPSC) technology, there presents a revolutionizing method for modeling complex human disorders. iPSCs are somatic cells that can be reprogrammed through the use of transcription factors to restore pluripotency. Directed differentiation is one of the ultimate goals for iPSC technology. The differentiated cells obtained from iPSCs can be used for transplantation to replace lost cells, for drug screening, or to model patient-specific disease mechanisms in vitro. For neuroscience research, human iPSC-derived neurons make an ideal model system for the study of neurological disorders and the development of neural functionality and plasticity. In the event of neurodegeneration, they can act as a therapeutically relevant source of cells for replacement purposes.