Remodeling Neurodegeneration: Somatic Cell Reprogramming-Based Models of Adult Neurological Disorders

Epigenetic reprogramming of adult human somatic cells to alternative fates, such as the conversion of human skin fibroblasts to induced pluripotency stem cells (iPSC), has enabled the generation of novel cellular models of CNS disorders. Cell reprogramming models appear particularly promising in the context of human neurological disorders of aging such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), for which animal models may not recapitulate key aspects of disease pathology. In addition, recent developments in reprogramming technology have allowed for more selective cell fate interconversion events, as from skin fibroblasts directly to diverse induced neuron (iN) subtypes. Challenges to human reprogramming-based cell models of disease are the heterogeneity of the human population and the extended temporal course of these disorders. A major goal is the accurate modeling of common nonfamilial “sporadic” forms of brain disorders.