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352 , 353 , 354 It is notable that these misfolded proteins may spread from the intestine to the CNS through the vagus nerve pathway, a process that is consistent with the Braak hypothesis on the pathological development of PD, namely, that the pathological changes of -synuclein may start in the intestine and then spread to the brain in a prion-like manner

Mechanistically, peroxynitrite has been shown to have 2 distinct mechanisms of action in its interaction with NOS: it can either uncouple the enzyme by oxidation of bound BH 4 or abolish enzymatic function by oxidative destruction of the NOS heme site, thus rendering an inactive enzyme, as opposed to one that is uncoupled 49,50