Fig. 7

Proposed pathophysiological mechanisms of the brain disease in Asl^Neo/Neo mice. a Residual coupled NOS produces NO with increased cGMP production. b Low l-arginine causes NOS uncoupling and produces superoxide ions (O₂⁻), which will generate the production of peroxynitrite (ONOO⁻). ONOO⁻ causes oxidative/nitrosative stress with production of nitrotyrosine and nitrite (NO₂⁻) after detoxification of ONOO⁻ by reduced glutathione (GSH). Oxidative/nitrosative stress will impair the respiratory chain, alter the energy production of the cell and lead to cell death. Neurons are particularly vulnerable as they cannot increase their production of glutathione adequately, and rely on an astrocytic supply. b Red arrows represent modified measured parameters in Asl^Neo/Neo compared to WT mice. This figure relies on data provided in this study and in the literature^{13,18,21,25,27} and discussed in the manuscript. cGMP cyclic guanosine monophosphate, GSH reduced glutathione, GSSG oxidised glutathione, NO nitric oxide, NO₂⁻ superoxide ion, ONO₂⁻ peroxynitrite, NOS nitric oxide synthase