title: Targeting autophagy in neurodegenerative diseases.
abstract: The most prevalent neurodegenerative disorders involve protein misfolding and the aggregation of specific proteins. Autophagy is becoming an attractive target to treat neurodegenerative disorders through the selective degradation of abnormally folded proteins by the lysosomal pathway. However, accumulating evidence indicates that autophagy impairment at different regulatory steps may contribute to the neurodegenerative process. Thus, a complex scenario is emerging where autophagy may play a dual role in neurodegenerative diseases by causing the downstream effect of promoting the degradation of misfolded proteins and an upstream effect where its deregulation perturbs global proteostasis, contributing to disease progression. Challenges in the future development of therapeutic strategies to target the autophagy pathway are discussed.
authors.affiliation: Neurounion Biomedical Foundation, CENPAR, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: rene.vidal@neurounion.com.
authors.forename: René L
authors.initials: RL
authors.lastname: Vidal
authors.affiliation: Neurounion Biomedical Foundation, CENPAR, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Soledad
authors.initials: S
authors.lastname: Matus
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.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bargsted
authors.affiliation: Neurounion Biomedical Foundation, CENPAR, Santiago, Chile; 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; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. Electronic address: chetz@med.uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy*
chemical_list: D051017:Apoptosis Regulatory Proteins
keywords: Beclin 1; aggregation; autophagy; mTOR; neurodegenerative disease; rapamycin