title: Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.
abstract: Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Menzies
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Angeleen
authors.initials: A
authors.lastname: Fleming
authors.affiliation: Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caricasole
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Carla F
authors.initials: CF
authors.lastname: Bento
authors.affiliation: Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Andrews
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Avraham
authors.initials: A
authors.lastname: Ashkenazi
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Jens
authors.initials: J
authors.lastname: Füllgrabe
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez Sanchez
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Cansu
authors.initials: C
authors.lastname: Karabiyik
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Floriana
authors.initials: F
authors.lastname: Licitra
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Lopez Ramirez
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Mariana
authors.initials: M
authors.lastname: Pavel
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Puri
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Renna
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ricketts
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Schlotawa
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Mariella
authors.initials: M
authors.lastname: Vicinanza
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Hyeran
authors.initials: H
authors.lastname: Won
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
authors.forename: John
authors.initials: J
authors.lastname: Skidmore
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK. Electronic address: dcr1000@cam.ac.uk.
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D009046:Motor Neurons / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011506:Proteins
keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; autophagy; dementia; lysosome; motor neuron disease; neurodegeneration; tau