title: Modeling ALS and FTD with iPSC-derived neurons.
abstract: Recent advances in genetics and neuropathology support the idea that amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTD) are two ends of a disease spectrum. Although several animal models have been developed to investigate the pathogenesis and disease progression in ALS and FTD, there are significant limitations that hamper our ability to connect these models with the neurodegenerative processes in human diseases. With the technical breakthrough in reprogramming biology, it is now possible to generate patient-specific induced pluripotent stem cells (iPSCs) and disease-relevant neuron subtypes. This review provides a comprehensive summary of studies that use iPSC-derived neurons to model ALS and FTD. We discuss the unique capabilities of iPSC-derived neurons that capture some key features of ALS and FTD, and underscore their potential roles in drug discovery. There are, however, several critical caveats that require improvements before iPSC-derived neurons can become highly effective disease models. This article is part of a Special Issue entitled SI: Exploiting human neurons.
authors.affiliation: Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0502, United States.
authors.forename: Sebum
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0502, United States; Pathology Service 113B, San Francisco VA Medical Center, 505 Parnassus Avenue, San Francisco, CA 94143-0502, United States. Electronic address: eric.huang2@ucsf.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Huang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D057180:Frontotemporal Dementia / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology*
keywords: Amyotrophic lateral sclerosis (ALS); Frontotemporal dementia (FTD); Frontotemporal lobar degeneration (FTLD); Induced pluripotent stem cells (iPSCs)