title: Adaptive preconditioning in neurological diseases - therapeutic insights from proteostatic perturbations.
abstract: In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a 'proteostasis network' and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge - the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson׳s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses and the molecular pathways they recruit might be exploited for therapeutic gain. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, F-69007, Lyon, France. Electronic address: bertrand.mollereau@ens-lyon.fr.
authors.forename: B
authors.initials: B
authors.lastname: Mollereau
authors.affiliation: Centre for Clinical Brain Sciences, Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom; Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, United Kingdom.
authors.forename: N M
authors.initials: NM
authors.lastname: Rzechorzek
authors.affiliation: Inserm, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, 14000 Caen, France.
authors.forename: B D
authors.initials: BD
authors.lastname: Roussel
authors.affiliation: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, F-69007, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Sedru
authors.affiliation: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, F-69007, Lyon, France.
authors.forename: D M
authors.initials: DM
authors.lastname: Van den Brink
authors.affiliation: INSERM U1065, C3M, Team 8 (Hepatic Complications in Obesity), Nice, France.
authors.forename: B
authors.initials: B
authors.lastname: Bailly-Maitre
authors.affiliation: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell, F-69007, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Palladino
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Molecular Studies of the Cell, Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: D B
authors.initials: DB
authors.lastname: Medinas
authors.affiliation: ITQB-UNL, Av. da Republica, EAN, 2780-157 Oeiras, Portugal.
authors.forename: P M
authors.initials: PM
authors.lastname: Domingos
authors.affiliation: Inserm, U 1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013 Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Hunot
authors.affiliation: Centre for Clinical Brain Sciences, Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Chandran
authors.affiliation: Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, CNRS UMR 8249, ESPCI ParisTech, PSL Research University, 75005 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Birman
authors.affiliation: ANSES, French Agency for Food, Environmental and Occupational Health & Safety, Neurodegenerative Diseases Unit, 31, avenue Tony Garnier, 69364 Lyon Cedex 07, France.
authors.forename: T
authors.initials: T
authors.lastname: Baron
authors.affiliation: Inserm, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, 14000 Caen, France.
authors.forename: D
authors.initials: D
authors.lastname: Vivien
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Faculty of Medicine, Rua Larga, and Department of Life Sciences, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: C B
authors.initials: CB
authors.lastname: Duarte
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Ryoo
authors.affiliation: Howard Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: H
authors.initials: H
authors.lastname: Steller
authors.affiliation: Washington University School of Medicine, Department of Internal Medicine, St. Louis, MO 63110 USA.
authors.forename: F
authors.initials: F
authors.lastname: Urano
authors.affiliation: Inserm ERL440 "Oncogenesis, Stress, Signaling", Université de Rennes 1, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Chevet
authors.affiliation: Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Cell Biology and Metabolomics platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France; INSERM, U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institute, Department of Women׳s and Children׳s Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: The Polak Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 30196, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Ciechanover
authors.affiliation: Department of Environmental Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA 01003, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Calabrese
authors.affiliation: Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kaufman
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Molecular Studies of the Cell, Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000818:Animals; D001343:Autophagy; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006801:Humans; D009422:Nervous System Diseases / Q000150:complications / Q000378:metabolism / Q000628:therapy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D057165:Proteostasis Deficiencies / Q000150:complications*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; ER stress; Glioblastoma; Hormesis; Ischemia; Parkinson׳s disease; Proteasome; Wolfram syndrome