HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS

Udai Bhan Pandey, Zhiping Nie, Yakup Batlevi, Brett A. McCray, Gillian P. Ritson, Natalia B. Nedelsky, Stephanie L. Schwartz, Nicholas A. DiProspero, Melanie A. Knight, Oren Schuldiner, Ranjani Padmanabhan, Marc Hild, Deborah L. Berry, Dan Garza, Charlotte C. Hubbert, Tso-Pang Yao, Eric H. Baehrecke and J. Paul Taylor ()
Additional contact information
Udai Bhan Pandey: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Zhiping Nie: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Yakup Batlevi: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA
Brett A. McCray: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Gillian P. Ritson: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Natalia B. Nedelsky: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Stephanie L. Schwartz: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Nicholas A. DiProspero: Neurogenetics Branch, NINDS, NIH, Bethesda, Maryland 20817, USA
Melanie A. Knight: Neurogenetics Branch, NINDS, NIH, Bethesda, Maryland 20817, USA
Oren Schuldiner: Stanford University, Stanford, California 94305, USA
Ranjani Padmanabhan: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA
Marc Hild: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA
Deborah L. Berry: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA
Dan Garza: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA
Charlotte C. Hubbert: Duke University, Durham, North Carolina 27710, USA
Tso-Pang Yao: Duke University, Durham, North Carolina 27710, USA
Eric H. Baehrecke: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA
J. Paul Taylor: University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

Nature, 2007, vol. 447, issue 7146, 860-864

Abstract: Autophagy to the rescue There are two main pathways that rid a cell of the protein misfits accumulated with time, the ubiquitin-proteasome system and autophagy, the self-destruction of a cell's own components through its lysosomal machinery. Work on a Drosophila model of neurodegenerative disease, in which the ubiquitin proteasome system breaks down, shows that autophagy can compensate for this loss. The two protein-destroying pathways are linked in vivo, with the microtubule-associated-histone deacetlyase HDAC6 acting as the link. Expression of HDAC6 is sufficient to induce autophagy and rescue neurodegeneration in the flies. These findings illuminate the relationship between autophagy and the ubiquitin-proteasome system, with implications for the pathogenesis and possible treatment of neurodegenerative proteopathies.

Date: 2007
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DOI: 10.1038/nature05853

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