Regulation of Neuronal Oxidative and Nitrosative Stress by Endogenous Protective Pathways and Disease Processes

Giles E. Hardingham, Stuart A. Lipton

Research output: Contribution to journalEditorialpeer-review


Oxidative/nitrosative stress contributes to the etiology of many neurological disorders in the developing and aged/mature central nervous system, including acute trauma such as ischemia and hyperoxia, as well as chronic diseases such as Alzheimer's and Parkinson's diseases. In addition to the accumulation of nonspecific oxidative damage, it is becoming clear that pathological conditions lead to the oxidative/nitrosative modification of specific proteins, including those involved in apoptosis, proteolysis, and protein (mis) folding. Several disorders, including stroke and Parkinson's disease, are associated with inactivating modifications of antioxidant enzymes themselves, thus compromising antioxidant defenses. Conversely, neuroprotective pathways, such as neurotrophin- and synaptic activity-induced signals, can upregulate key antioxidant systems, potentially contributing to the cytoprotective actions of adaptive stress responses following exercise or calorie-restriction. On the flip-side, hypofunction of these pathways is associated with the death of developing neurons. An increased knowledge of how neuronal antioxidant systems are controlled in health and disease is unearthing therapeutic targets in several disorders. Moreover, the emerging importance of master regulators of antioxidant defenses such as nuclear factor-erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-g coactivator 1 alpha (PGC-1 alpha) is revealing ways through which intrinsic defenses may be manipulated to combat oxidative/nitrosative stress. Such approaches offer an alternative strategy to classical antioxidant interventions based on the administration of free radical scavengers and spin-traps. Antioxid. Redox Signal. 14, 1421-1424.

Original languageEnglish
Pages (from-to)1421-1424
Number of pages4
JournalAntioxidants and Redox Signaling
Issue number8
Publication statusPublished - Apr 2011

Cite this