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GSK-3α/β kinases and amyloid production in vivo

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A Brief Communications Arising to this article was published on 07 December 2011

Abstract

Arising from C. J. Phiel, C. A. Wilson, V. M.-Y. Lee & P. S. Klein Nature 423, 435–439 (2003)10.1038/nature01640

A major unresolved issue in Alzheimer’s disease is identifying the mechanisms that regulate proteolytic processing of amyloid precursor protein (APP)—glycogen synthase kinase-3 (GSK-3) isozymes are thought to be important in this regulation. Phiel et al.1 proposed that GSK-3α, but not GSK-3β, controls production of amyloid1. We analysed the proteolytic processing of mouse and human APP in mouse brain in vivo in five different genetic and viral models. Our data do not yield evidence for either GSK-3α-mediated or GSK-3β-mediated control of APP processing in brain in vivo.

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Figure 1: APP processing in the brains of Gsk3a n−/− and Gsk3a KO mice.
Figure 2: APP processing in the brains of Gsk3b n−/− mice.

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Author notes

  1. Present addresses: FARL-Institute of Neurosciences, UC Louvain, B-1000 Brussels, Belgium (I.D.); Laboratory of Ion Channel Research, KU Leuven, B-3000 Leuven, Belgium (M.G.)

Authors and Affiliations

  1. Experimental Genetics Group, KU Leuven, Leuven, Belgium

    Tomasz Jaworski, Ilse Dewachter, Benoit Lechat, Maarten Gees, Anna Kremer, David Demedts, Peter Borghgraef, Herman Devijver & Fred Van Leuven

  2. Department of Neurology, Georg-August-University, Göttingen, Germany

    Seb Kügler

  3. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

    Satish Patel & Jim R. Woodgett

Authors
  1. Tomasz Jaworski
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  2. Ilse Dewachter
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  3. Benoit Lechat
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  4. Maarten Gees
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  5. Anna Kremer
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  6. David Demedts
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  7. Peter Borghgraef
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  8. Herman Devijver
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  9. Seb Kügler
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  10. Satish Patel
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  11. Jim R. Woodgett
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  12. Fred Van Leuven
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Contributions

Generation of transgenic and knockout mice, B.L., D.D., H.D., S.P. and J.R.W.; generation of AAV vectors and intracerebral injections, T.J., D.D. and S.K.; brain analysis, T.J., I.D., B.L., M.G., A.K. and P.B.; design of experiments, data analysis and figures, T.J., I.D., P.B. and F.V.L.; writing of manuscript, T.J. and F.V.L. T.J., I.D. and B.L. contributed equally to this work.

Corresponding author

Correspondence to Fred Van Leuven.

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Competing financial interests: declared none.

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Jaworski, T., Dewachter, I., Lechat, B. et al. GSK-3α/β kinases and amyloid production in vivo. Nature 480, E4–E5 (2011). https://doi.org/10.1038/nature10615

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