title: ALS: A bucket of genes, environment, metabolism and unknown ingredients.
abstract: The scientific scenario of amyotrophic lateral sclerosis (ALS) has dramatically changed since TDP-43 aggregates were discovered in 2006 as the main component of the neuronal inclusions seen in the disease, and more recently, when the implication of C9ORF72 expansion in familial and sporadic cases of ALS and frontotemporal dementia was confirmed. These discoveries have enlarged an extense list of genes implicated in different cellular processes such as RNA processing or autophagia among others and have broaden the putative molecular targets of the disease. Some of ALS-related genes such as TARDBP or SOD1 among others have important roles in the regulation of glucose and fatty acids metabolism, so that an impairment of fatty acids (FA) consumption and ketogenic deficits during exercise in ALS patients would connect the physiopathology with some of the more intriguing epidemiological traits of the disease. The current understanding of ALS as part of a continuum with other neurodegenerative diseases and a crossroads between genetic, neurometabolic and environmental factors represent a fascinating model of interaction that could be translated to other neurodegenerative diseases. In this review we summarize the most relevant data obtained in the ten last years and the key lines for future research in ALS.
authors.affiliation: Neuroscience Area, Biodonostia Health Research Institute, San Sebastián, Gipuzkoa, 20014, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Zufiría
authors.affiliation: Neuroscience Area, Biodonostia Health Research Institute, San Sebastián, Gipuzkoa, 20014, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain; Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Huddinge, 14157, Sweden.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Gil-Bea
authors.affiliation: Neuroscience Area, Biodonostia Health Research Institute, San Sebastián, Gipuzkoa, 20014, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain; Neuromuscular Disorders Unit, Neurology Department, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain; ALS Multidisciplinary Unit, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernández-Torrón
authors.affiliation: Neuroscience Area, Biodonostia Health Research Institute, San Sebastián, Gipuzkoa, 20014, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain; Neuromuscular Disorders Unit, Neurology Department, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain; ALS Multidisciplinary Unit, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Poza
authors.affiliation: ALS-Neuromuscular Unit, Department of Neurology, Hospital Gregorio Marañón, Madrid, 28007, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Muñoz-Blanco
authors.affiliation: Neuromuscular Disorders Unit, Department of Neurology, Universitat Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, 08026, Spain; Centro de Investigación Básica en Red en Enfermedades Raras (CIBERER), Madrid, 28029, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-García
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain; Service of Neurology, University Hospital Marques de Valdecilla, Institute of Investigation Valdecilla (IDIVAL), 39008, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Riancho
authors.affiliation: Neuroscience Area, Biodonostia Health Research Institute, San Sebastián, Gipuzkoa, 20014, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Ministry of Economy and Competitiveness, Madrid, 28031, Spain; Neuromuscular Disorders Unit, Neurology Department, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain; ALS Multidisciplinary Unit, Hospital Donostia, San Sebastián, Gipuzkoa, 20014, Spain; Department of Neurosciences, School of Medicine, University of the Basque Country (EHU-UPV), San Sebastián, Gipuzkoa, 20014, Spain. Electronic address: adolfo.lopezdemunainarregui@osakidetza.eus.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D059647:Gene-Environment Interaction; D006801:Humans
keywords: Amyotrophic lateral sclerosis; Environmental factors; Genetics; Metabolism; Neurodegeneration; Toxins