Evidence of increased oxidative stress has been found in various neurodegenerative diseases and conditions. While it is unclear whether oxidative stress is a cause or effect, protein, lipid, and DNA have all been found to be susceptible to oxidant-induced modifications that alter their function. Results of clinical trials based on the oxidative-stress theory have been mixed, though data continues to indicate that prevention of high levels of oxidative stress is beneficial for health and increases longevity. Due to the highly reactive nature of the sulfhydryl group, the focus of this paper is on the impact of oxidative stress on cysteine-dependent enzymes and how oxidative stress may contribute to neurological dysfunction through this selected group of proteins. 1. Introduction It is clear that while oxygen is essential for life in order to produce chemical energy in the form of ATP, paradoxically, the byproduct of its metabolism generates multiple reactive oxygen species (ROS) that are associated with cellular toxicity. Specifically, in regards to neurodegeneration, there is substantial evidence that ROS are a major component of diseases including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis [1–4]. While clinical trials aimed at decreasing the burden of oxidative stress have not clearly demonstrated effectiveness, genetic research has found that high levels of antioxidant enzymes prolong life and decrease pathology. In addition, animal models have also indicated that oxidative stress is an important and consistent characteristic of many forms of neurodegeneration. One particular group of proteins that appear to be intimately involved in the neurodegenerative processes is the cysteine-dependent proteins. This group includes various proteases, antioxidant enzymes, kinases, phosphatases, and other types of enzymes as well as other nonenzymatic proteins such as those that use cysteine as a structural component rather than as part of a catalytic site. More research will be needed to firmly establish the extent to which oxidative stress is causal in these diseases, but based on current understanding, therapies to reverse the oxidant-induced modifications of proteins, lipids or, DNA are expected to be beneficial. This paper will highlight some selected, yet significant cysteine-dependent enzymatic systems that rely on a proper redox environment for their activity and provide evidence for their redox control in neurodegenerative disease. Potential relationships to cancers will also be discussed. 2. Redox Sensitivity of Cysteine The aminoacid
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