NO mediated neurotoxicity: redox changes and energy failure in a neuroinflammatory model

The nefarious role of NO in neurodegenerative diseases such as Alzheimer's disease stems from the excessive production and labile nature of NO. The mechanisms of NO redox signaling through protein post translational modification is ill-defined in the neurodegenerative model. S-nitrosylation, which can be an intermediary step leading S-glutathionylation of proteins has emerged as a well characterized mechanism through which NO reversibly regulates cell function. However, there is little evidence concerning the regulation of S-glutathionylation of proteins by NO, which proteins are glutathionylated in neurons during nitrosative stress, and the consequence of glutathionylation of proteins on overall cellular and mitochondrial function. Therefore, the hypothesis to be tested is that nitric oxide generated during neuroinflammation leads to changes in cellular redox status and protein post translational modification which play a role in energy impairment leading to neuronal injury.