Modeling Human Neurological Diseases
The limited access to patient neurons greatly impedes the progress of research in neurological diseases. Reprogramming of human neurons from adult fibroblasts provides an unprecedented approach to deciphering the molecular pathogenesis underlying disease conditions. Using lentiviral delivery of transcription factors, we can generate human neurons from adult fibroblast via two strategies. One strategy is the direct conversion of fibroblasts into neurons (for example, directly induced motor neurons, diMNs). The other strategy is induced pluripotent stem cells (iPSCs)-based reprogramming and differentiation (for example, iPSC-MNs). Using these patient-specific neurons, research efforts are focusing on the molecular and cellular pathophysiology of neurological disorders, such as Alzheimer disease (AD), Dystonia and amyotrophic lateral sclerosis (ALS).