title: The ER proteostasis network in ALS: Determining the differential motoneuron vulnerability.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal late-onset neurodegenerative disease characterized by the selective loss of motoneurons. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting abnormal protein aggregation and altered mRNA metabolism as common phenomena. ALS involves the selective vulnerablility of a subpopulation of motoneurons, suggesting that intrinsic factors may determine ALS pathogenesis. Accumulating evidence indicates that alterations to endoplasmic reticulum (ER) proteostasis play a critical role on disease progression, representing one of the earliests pathological signatures of the disease. Here we discuss recent studies uncovering a fundamental role of ER stress as the driver of selective neuronal vulnerability in ALS and discuss the potential of targeting the unfolded protein response (UPR) as a therapeutic strategy to treat ALS.
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago 8380453, Chile; Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rozas
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago 8380453, Chile; Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bargsted
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago 8380453, Chile; Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Martínez
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago 8380453, Chile; Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, USA; Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: chetz@med.uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago 8380453, Chile; Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile. Electronic address: dmedinas@med.uchile.cl.
authors.forename: Danilo B
authors.initials: DB
authors.lastname: Medinas
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000294:innervation; D066329:Protein Aggregates; D017510:Protein Folding; D020543:Proteome / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; D066329:Protein Aggregates; D020543:Proteome
keywords: ALS; Chaperones; ER stress; Proteostasis; Selective vulnerability