title: Advances in cellular models to explore the pathophysiology of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is fatal for most patients less than 3 years from when the first symptoms appear. The aetiologies for sporadic and most familial forms of ALS are unknown, but genetic factors are increasingly recognized as causal in a subset of patients. Studies of disease physiology suggest roles for oxidative stress, glutamate-mediated excitotoxicity or protein aggregation; how these pathways interact in the complex pathophysiology of ALS awaits elucidation. Cellular models are being used to examine disease mechanisms. Recent advances include the availability of expanded cell types, from neuronal or glial cell culture to motoneuron-astrocyte co-culture genetically or environmentally modified. Cell culture experiments confirmed the central role of glial cells in ALS. The recent adaptation of induced pluripotent stem cells (iPSC) for ALS modeling could allow a broader perspective and is expected to generate new hypotheses, related particularly to mechanisms underlying genetic factors. Cellular models have provided meaningful advances in the understanding of ALS, but, to date, complete characterization of in vitro models is only partially described. Consensus on methodological approaches, strategies for validation and techniques that allow rapid adaptation to new genetic or environmental influences is needed. In this article, we review the principal cellular models being employed in ALS and highlight their contribution to the understanding of disease mechanisms. We conclude with recommendations on means to enhance the robustness and generalizability of the different concepts for experimental ALS.
authors.affiliation: Equipe « Neurogénétique et neurométabolomique », Université François-Rabelais de Tours, UMR INSERM U930, 37032, Tours, France, charlotte.veyrat@live.fr.
authors.forename: C
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: P
authors.initials: P
authors.lastname: Corcia
authors.forename: A
authors.initials: A
authors.lastname: Dangoumau
authors.forename: F
authors.initials: F
authors.lastname: Laumonnier
authors.forename: E
authors.initials: E
authors.lastname: Piver
authors.forename: P H
authors.initials: PH
authors.lastname: Gordon
authors.forename: C R
authors.initials: CR
authors.lastname: Andres
authors.forename: P
authors.initials: P
authors.lastname: Vourc'h
authors.forename: H
authors.initials: H
authors.lastname: Blasco
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology