L-Norvaline is a non-proteinogenic amino acid, an isomer of valine, and an inhibitor of arginase and p70 ribosomal S6 kinase 1 (p70S6K1) kinase.1,2 It inhibits arginase-mediated urea production in J774A.1 macrophage lysates when used at a concentration of 10 mM and TNF-α-induced p70S6K1 activation in human umbilical vein endothelial cells (HUVECs) at 20 mM.1 L-Norvaline reduces microgliosis and the level of amyloid-β fibrils in the hippocampus, as well as improves learning and memory in the Morris water maze in the 3xTg mouse model of Alzheimer’s disease.3
1.Chang, C.-I., Liao, J.C., and Kuo, L.Arginase modulates nitric oxide production in activated macrophagesAm. J. Physiol.274(1)H342-H348(1998) 2.Ming, X.-F., Rajapakse, A.G., Carvas, J.M., et al.Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvalineBMC Cardiovasc. Disord.912(2009) 3.Polis, B., Srikanth, K.D., Elliott, E., et al.L-Norvaline reverses cognitive decline and synaptic loss in a murine model of Alzheimer's diseaseNeurotherapeutics15(4)1036-1054(2018)