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Autophagy gone awry in neurodegenerative diseases

Nature Neuroscience volume 13, pages 805–811 (2010)Cite this article

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Abstract

Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.

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Figure 1: Possible steps of macroautophagy altered in neurodegeneration.
Figure 2: Cross-talk among macroautophagy and different cellular proteolytic systems.
Figure 3: Variations of the macroautophagic process.

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Acknowledgements

We thank the numerous colleagues in the field of autophagy who through their animated discussions have helped shape this review and S. Kaushik and S. Orenstein for critically reading the manuscript. Work in our laboratory is supported by US National Institutes of Health grants from the National Institute on Aging (AG021904, AG031782), the National Institute of Diabetes and Digestive and Kidney Diseases (DK041918), the National Institute of Neurological Disorders and Stroke (NS038370), a Glenn Foundation Award and a Hirsch/Weill-Caulier Career Scientist Award. E.W. is supported by a Hereditary Disease Foundation Fellowship.

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  1. Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA

    Esther Wong & Ana Maria Cuervo

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Correspondence to Ana Maria Cuervo.

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Wong, E., Cuervo, A. Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13, 805–811 (2010). https://doi.org/10.1038/nn.2575

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