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Nitric Oxide Decreases the Enzymatic Activity of Insulin Degrading Enzyme in APP/PS1 Mice

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Abstract

Nitric oxide has been implicated in the regulation of enzyme activity, particularly the activity of metalloproteinases. Since the inducible form of the nitric oxide synthase (NOS2), is upregulated in Alzheimer’s disease, we investigated the activity of two amyloid β degrading enzymes, IDE and neprilysin. In vitro we demonstrated that the activity of IDE was inhibited by *NO donor Sin-1, whereas activity of neprilysin remained unaffected. In vivo the activity of insulin-degrading enzyme was lowered in APP/PS1 mice, but not in APP/PS1/NOS2(−/−) mice. These data suggest that NOS2 upregulation impairs amyloid β degradation through negative regulation of IDE activity and thus loss of NOS2 activity will positively influence amyloid β clearance.

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Abbreviations

AEBSF:

4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride

PN:

Peroxynitrate

Sin-1:

3-morpholino-sydnonimine

DetaNONOate:

(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate

GSNO:

S-Nitrosoglutathione

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Clinical Neurosciences Unit, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany

    Markus P. Kummer, Claudia Hülsmann, Michael Hermes, Daisy Axt & Michael T. Heneka

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  1. Markus P. Kummer
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  2. Claudia Hülsmann
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  3. Michael Hermes
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  4. Daisy Axt
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  5. Michael T. Heneka
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Corresponding author

Correspondence to Michael T. Heneka.

Additional information

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (HE 3350/4-1,4-2) to MTH.

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Kummer, M.P., Hülsmann, C., Hermes, M. et al. Nitric Oxide Decreases the Enzymatic Activity of Insulin Degrading Enzyme in APP/PS1 Mice. J Neuroimmune Pharmacol 7, 165–172 (2012). https://doi.org/10.1007/s11481-011-9339-7

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  • DOI: https://doi.org/10.1007/s11481-011-9339-7

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