title: Patient-derived olfactory mucosa for study of the non-neuronal contribution to amyotrophic lateral sclerosis pathology.
abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease which currently has no cure. Research using rodent ALS models transgenic for mutant superoxide dismutase 1 (SOD1) has implicated that glial-neuronal interactions play a major role in the destruction of motor neurons, but the generality of this mechanism is not clear as SOD1 mutations only account for less than 2% of all ALS cases. Recently, this hypothesis was backed up by observation of similar effects using astrocytes derived from post-mortem spinal cord tissue of ALS patients which did not carry SOD1 mutations. However, such necropsy samples may not be easy to obtain and may not always yield viable cell cultures. Here, we have analysed olfactory mucosa (OM) cells, which can be easily isolated from living ALS patients. Disease-specific changes observed when ALS OM cells were co-cultured with human spinal cord neurons included decreased neuronal viability, aberrant neuronal morphology and altered glial inflammatory responses. Our results show the potential of OM cells as new cell models for ALS.
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa" (C.S.I.C.- U.A.M.), Universidad Autónoma de Madrid, Madrid, Spain.
authors: Vega
authors: V
authors: García-Escudero
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: María
authors: M
authors: Rosales
authors: Departamento de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: José Luis
authors: JL
authors: Muñoz
authors: Departamento de Otorrinolaringología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Esteban
authors: E
authors: Scola
authors: Departamento de Otorrinolaringología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Javier
authors: J
authors: Medina
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Hena
authors: H
authors: Khalique
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Guillermo
authors: G
authors: Garaulet
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Antonio
authors: A
authors: Rodriguez
authors: Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Filip
authors: F
authors: Lim
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009831:Olfactory Mucosa / Q000378:metabolism / Q000473:pathology*; D061251:Primary Cell Culture; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C000606290:SOD1 protein, human; D014746:Vimentin; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: SOD-1 neurotoxicity; amyotrophic lateral sclerosis; inflammation-responsive promoter; non-cell autonomous toxicity; olfactory mucosa