Thiol-protease oxidation in age-related neuropathology |
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Authors: | Guttmann Rodney P Ghoshal Sarbani |
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Institution: | Department of Gerontology, Department of Physiology, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA |
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Abstract: | Increased oxidative stress is a hallmark of every major neurodegenerative disease that has been studied. Numerous biomarkers of oxidative stress have been found, indicating that waves of oxidation had, at one time or another, overwhelmed antioxidant defenses, leaving behind a host of oxidized DNA, lipids, and proteins in their path. Although some level of oxidation may be beneficial, perhaps mediated by a hormetic response, the extent and types of oxidation detected in neuropathological states would suggest that oxidative stress contributes to a loss of homeostasis and cellular dysfunction. Although there are many targets of oxidants, this review emphasizes protein oxidation with a focus on an important group of redox-sensitive enzymes, the thiol-proteases. Both the direct and the indirect effects of oxidation and their potential importance in neurodegeneration are considered. |
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Keywords: | AD Alzheimer disease Atg autophagin IDE insulysin MJD Machado-Joseph disease MMP matrix metalloproteinase NEP neprilysin PD Parkinson disease SENP sentrin-specific protease SUMO small-ubiquitin modifier TIMP-1 tissue inhibitor of metalloproteinase-1 UCHL1 ubiquitin carboxy-terminal hydrolase L1 |
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