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.

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Mutations in MAPT cause a variety of neurodegenerative disorders. Lopez et al. confirm that A152T-variant tau is associated with increased risk for frontotemporal dementia and progressive supranuclear palsy syndrome. Upregulation of autophagy increases tau clearance and ameliorates pathology in zebrafish expressing A152T-tau, suggesting potential for the treatment of tauopathies.