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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Online
ISSN
1437-4315
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Volume 387, Issue 7 (Jul 2006)

Issues

Inhibition of calcineurin by infusion of CsA causes hyperphosphorylation of tau and is accompanied by abnormal behavior in mice

Da-yu Yu
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China
/ Jing Luo
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China
/ Fan Bu
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China
/ Gao-jie Song
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China
/ Lai-qun Zhang
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China and Shijiazhuang Pharmaceutical Group Company, Shijiazhuang 050051, China
/ Qun Wei
  • Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, China
Published Online: 2006-07-20 | DOI: https://doi.org/10.1515/BC.2006.121

Abstract

Calcineurin is a Ca2+/calmodulin-dependent phosphatase that dephosphorylates numerous substrates in different neuronal compartments. Genetic and pharmacological studies have provided insight into its involvement in the brain. Cyclosporin A (CsA) is used as a specific calcineurin inhibitor in many pharmacological experiments. However, the calcineurin activity of CsA-treated brain has not been reported. To examine the relationship between calcineurin activity and brain function, we injected CsA into the left lateral ventricle of the mouse brain and assayed calcineurin activity. CsA reduced calcineurin activity in a dose-dependent manner, without affecting the amount of calcineurin protein. Assays of the effect of protein phosphatase inhibitors on CsA-injected mouse brain extracts and kinetic analysis revealed that CsA inhibited calcineurin activity in a non-competitive manner in vivo, in agreement with in vitro results. Injection of CsA led to enhanced phosphorylation of tau at Ser-262 (12E8 site), Ser-198, Ser-199, and/or Ser-202 (Tau-1 site) and Ser-396 and/or Ser-404 (PHF-1 site), as well as to impaired spatial memory, which are two characteristic features of Alzheimer's disease. We propose that inhibition of calcineurin may play an important role in Alzheimer's disease.

Keywords: activity; calcineurin; cyclosporin A; spatial memory; tau

References

About the article

Corresponding author


Received: January 19, 2006

Accepted: March 29, 2006

Published Online: 2006-07-20

Published in Print: 2006-07-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.121. Export Citation

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