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Neuroprotection by Radical Avoidance: Search for Suitable Agents
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Berliner str. 28, D-37073 Göttingen, Germany
Received: 12 November 2009; in revised form: 30 November 2009 / Accepted: 4 December 2009 / Published: 7 December 2009
Abstract: Neurodegeneration is frequently associated with damage by free radicals. However, increases in reactive oxygen and nitrogen species, which may ultimately lead to neuronal cell death, do not necessarily reflect its primary cause, but can be a consequence of otherwise induced cellular dysfunction. Detrimental processes which promote free radical formation are initiated, e.g., by disturbances in calcium homeostasis, mitochondrial malfunction, and an age-related decline in the circadian oscillator system. Free radicals generated at high rates under pathophysiological conditions are insufficiently detoxified by scavengers. Interventions at the primary causes of dysfunction, which avoid secondary rises in radical formation, may be more efficient. The aim of such approaches should be to prevent calcium overload, to reduce mitochondrial electron dissipation, to support electron transport capacity, and to avoid circadian perturbations. l-Theanine and several amphiphilic nitrones are capable of counteracting excitotoxicity and/or mitochondrial radical formation. Resveratrol seems to promote mitochondrial biogenesis. Mitochondrial effects of leptin include attenuation of electron leakage. Melatonin combines all the requirements mentioned, additionally regulates anti- and pro-oxidant enzymes and is, with few exceptions, very well tolerated. In this review, the perspectives, problems and limits of drugs are compared which may be suitable for reducing the formation of free radicals.
Keywords: electron leakage; free radicals; melatonin; mitochondrial metabolism modifiers; nitrones
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MDPI and ACS Style
Hardeland, R. Neuroprotection by Radical Avoidance: Search for Suitable Agents. Molecules 2009, 14, 5054-5102.
Hardeland R. Neuroprotection by Radical Avoidance: Search for Suitable Agents. Molecules. 2009; 14(12):5054-5102.
Hardeland, Rüdiger. 2009. "Neuroprotection by Radical Avoidance: Search for Suitable Agents." Molecules 14, no. 12: 5054-5102.