[en] 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.
Disciplines :
Neurology
Author, co-author :
Kummer, Markus P; Clinical Neurosciences Unit, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
Hülsmann, Claudia; Clinical Neurosciences Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany
Hermes, Michael; Clinical Neurosciences Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany
Axt, Daisy; Clinical Neurosciences Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany
HENEKA, Michael ; Clinical Neurosciences Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Nitric oxide decreases the enzymatic activity of insulin degrading enzyme in APP/PS1 mice.
Publication date :
March 2012
Journal title :
Journal of Neuroimmune Pharmacology
ISSN :
1557-1890
eISSN :
1557-1904
Publisher :
Springer Science and Business Media LLC, United States
This study was supported by a grant from the Deutsche Forschungsgemeinschaft (HE 3350/4-1,4-2) to MTH. M.P.Kummer.C.Hülsmann.M.Hermes.D.Axt. M. T. Heneka (*) Clinical Neurosciences Unit, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany e-mail: michael.heneka@ukb.uni-bonn.de
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