ALS: A bucket of genes, environment, metabolism and unknown ingredients
Por:
Zufiria, M, Gil-Bea, FJ, Fernandez-Torron, R, Poza, JJ, Munoz-Blanco, JL, Rojas-Garcia, R, Riancho, J, de Munain, AL
Publicada:
1 jul 2016
Resumen:
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. (C) 2016 Elsevier Ltd. All rights reserved.
Filiaciones:
Zufiria, M:
Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian 20014, Gipuzkoa, Spain
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Gil-Bea, FJ:
Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian 20014, Gipuzkoa, Spain
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, S-14157 Huddinge, Sweden
Fernandez-Torron, R:
Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian 20014, Gipuzkoa, Spain
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Hosp Donostia, Dept Neurol, Neuromuscular Disorders Unit, San Sebastian 20014, Gipuzkoa, Spain
Hosp Donostia, ALS Multidisciplinary Unit, San Sebastian 20014, Gipuzkoa, Spain
Poza, JJ:
Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian 20014, Gipuzkoa, Spain
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Hosp Donostia, Dept Neurol, Neuromuscular Disorders Unit, San Sebastian 20014, Gipuzkoa, Spain
Hosp Donostia, ALS Multidisciplinary Unit, San Sebastian 20014, Gipuzkoa, Spain
Munoz-Blanco, JL:
Hosp Gregorio Maranon, Dept Neurol, ALS Neuromuscular Unit, Madrid 28007, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Dept Neurol, Hosp Santa Creu & St Pau, Neuromuscular Disorders Unit, Barcelona 08026, Spain
Ctr Invest Basica Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Riancho, J:
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Univ Hosp Marques de Valdecilla, Inst Invest Valdecilla IDIVAL, Serv Neurol, Santander 39008, Spain
de Munain, AL:
Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian 20014, Gipuzkoa, Spain
Inst Salud Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
Hosp Donostia, Dept Neurol, Neuromuscular Disorders Unit, San Sebastian 20014, Gipuzkoa, Spain
Hosp Donostia, ALS Multidisciplinary Unit, San Sebastian 20014, Gipuzkoa, Spain
Univ Basque Country, UPV EHU, Dept Neurosci, Sch Med, San Sebastian 20014, Gipuzkoa, Spain
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