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Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease

Author

Listed:
  • Gen He

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • Wenjie Luo

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • Peng Li

    (Intra-Cellular Therapies, Inc., Audubon Biomedical Science and Technology Park, 3960 Broadway, New York, New York 10032, USA)

  • Christine Remmers

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • William J. Netzer

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • Joseph Hendrick

    (Intra-Cellular Therapies, Inc., Audubon Biomedical Science and Technology Park, 3960 Broadway, New York, New York 10032, USA)

  • Karima Bettayeb

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • Marc Flajolet

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

  • Fred Gorelick

    (Yale University School of Medicine
    VA Connecticut Healthcare, 333 Cedar Street)

  • Lawrence P. Wennogle

    (Intra-Cellular Therapies, Inc., Audubon Biomedical Science and Technology Park, 3960 Broadway, New York, New York 10032, USA)

  • Paul Greengard

    (Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA)

Abstract

New Alzheimer's target Much of the work on potential anti-Alzheimer's disease drugs has been focused on compounds that reduce the accumulation of neurotoxic amyloid-β peptide in the brain. This has met with little success, in part because agents that block γ-secretase also block processing of Notch, a signalling protein essential for many homeostatic functions, resulting in severe side effects. Now the discovery of a γ-secretase activating protein (GSAP) that selectively controls amyloid-β generation without influencing Notch cleavage suggests a possible new target for anti-Alzheimer's drugs. The anticancer drug imatinib (Gleevec), known to inhibit amyloid-β formation without affecting Notch cleavage, is shown to act via an effect on GSAP. This suggests that GSAP inhibitors that can cross the blood–brain barrier (unlike imatinib) may hold promise for treating Alzheimer's disease.

Suggested Citation

  • Gen He & Wenjie Luo & Peng Li & Christine Remmers & William J. Netzer & Joseph Hendrick & Karima Bettayeb & Marc Flajolet & Fred Gorelick & Lawrence P. Wennogle & Paul Greengard, 2010. "Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease," Nature, Nature, vol. 467(7311), pages 95-98, September.
    • Handle: RePEc:nat:nature:v:467:y:2010:i:7311:d:10.1038_nature09325
    DOI: 10.1038/nature09325
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