Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its Relevance to Neurodegenerative Diseases

Figure 1

Imbalance in oxidant production and antioxidant mechanisms contributes to neurodegeneration. Under physiological conditions, antioxidant mechanisms such as cysteine-based redox regulation (Prx, Grx, Trx, glutathione (GSH), etc.), as well as transcriptional pathways represented by Keap1/Nrf2 and Hsp90/HSF1, maintain low concentrations of ROS/RNS in the neurons. These low levels of oxidants activate specific signaling pathways that subserve normal cell signaling and in fact may be neuroprotective in nature. On the other hand, under pathological situations, including AD and PD, there is a decrease in antioxidant mechanisms and increased oxidant production, effectively creating high levels of ROS/RNS. Oxidative/nitrosative stress generated in this manner can contribute to cell damage and results in neurodegeneration.