Figure 8.

A proposed model of the function of the S-nitrosylated PARIS in dopaminergic neurons. PARIS can be S-nitrosylated at cysteine 265 (C265), and S-nitrosylated PARIS translocates to the insoluble fraction, leading to the sequestration of PGC-1α into insoluble deposits. In the sporadic PD model, α-synuclein preformed fibrils (α-syn PFFs)-injected mice, we found an increase in S-nitrosylated PARIS and insoluble sequestration of PGC-1α in substantia nigra (SN), resulting in mitochondrial abnormailities and DA neuronal death that were restored by N(ω)-nitro-L-arginine methyl ester (L-NAME). These results suggest that modulation of NO can be a therapeutic for α-syn PFFs-mediated neurodegeneration.