title: Gene therapy to target ER stress in brain diseases.
abstract: Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valenzuela
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Martínez
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Duran-Aniotz
authors.affiliation: Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Immunology and Infectious diseases, Harvard School of Public Health, 02115 Boston, MA, USA. Electronic address: clahetz@med.uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000235:genetics / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D056811:Unfolded Protein Response / Q000235:genetics
keywords: Alzheimer's disease; Amyotrophic lateral sclerosis; Endoplasmic reticulum stress; Gene therapy; Parkinson's disease; Unfolded protein response