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

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  • 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)

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.

Suggested Citation

  • 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 & Ranj, 2007. "HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS," Nature, Nature, vol. 447(7146), pages 860-864, June.
    • Handle: RePEc:nat:nature:v:447:y:2007:i:7146:d:10.1038_nature05853
    DOI: 10.1038/nature05853
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    Cited by:

    1. Maria Angeles Fernandez-Estevez & Maria Jose Casarejos & Jose López Sendon & Juan Garcia Caldentey & Carolina Ruiz & Ana Gomez & Juan Perucho & Justo García de Yebenes & Maria Angeles Mena, 2014. "Trehalose Reverses Cell Malfunction in Fibroblasts from Normal and Huntington's Disease Patients Caused by Proteosome Inhibition," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-9, February.
    2. Amanda M. Gleixner & Brandie Morris Verdone & Charlton G. Otte & Eric N. Anderson & Nandini Ramesh & Olivia R. Shapiro & Jenna R. Gale & Jocelyn C. Mauna & Jacob R. Mann & Katie E. Copley & Elizabeth , 2022. "NUP62 localizes to ALS/FTLD pathological assemblies and contributes to TDP-43 insolubility," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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