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Neuron. 2017 Mar 8;93(5):1015-1034. doi: 10.1016/j.neuron.2017.01.022.

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.

Author information

1
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.
2
Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
3
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.

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.

KEYWORDS:

Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; autophagy; dementia; lysosome; motor neuron disease; neurodegeneration; tau

PMID:
28279350
DOI:
10.1016/j.neuron.2017.01.022
[Indexed for MEDLINE]
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