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The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the β-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 μm significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.

The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the beta-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 mum significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.