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

作者：Kummer Markus P; Huelsmann Claudia; Hermes Michael; Axt Daisy; Heneka Michael T^*

来源：Journal of Neuroimmune Pharmacology, 2012, 7(1): 165-172.

DOI：10.1007/s11481-011-9339-7

• IDE
• Insulin degrading enzyme
• Nitric oxide
• A beta
• Nitration

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%26apos;s disease, we investigated the activity of two amyloid beta 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 beta degradation through negative regulation of IDE activity and thus loss of NOS2 activity will positively influence amyloid beta clearance.

• 出版日期2012-3