Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · 2002 · 10 citations · 0 references
Life SciencesNeurobiologyNeuroscienceAgingCellular NeuroscienceNeurodegenerationAmyotrophic Lateral SclerosisNeurodegenerative DiseasesNeurodegenerative DisordersNeuropathology Of AgingNeuroprotectionOxidative StressAge-related Oxidative StressNeuronal VulnerabilityOxidative Stress - Induced NeurotoxicityOxidative Stress InjuryOxidative Stress NeurotoxicityOxidative Stress ToxicityReactive Oxygen Species InjurySublethal Toxicity
BACKGROUND: An increase in reactive oxygen species (ROS) burden and subsequent oxidative damage to nucleic acids, proteins, and lipids, occurs during the normal aging process of cells, including neurons. OBJECTIVE: With this in mind we hypothesize that an oxidative stress which leads to an increased state of oxidation, but is not itself lethal, nonetheless renders the motor neuron more vulnerable to other sublethal stressors. METHOD AND RESULTS: We have combined paraquat-induced oxidative stress with sublethal increased exogenous glutamate, or thermal stress, or a combination of both, and demonstrate a synergistic effect of low-level stressors on the viability of motor neurons. CONCLUSION: This model of low-level oxidative stress reveals the subsequent vulnerability of motor neurons to genetic or environmental stressors and may in part explain the mid-life/late-life symptom onset in both familial and sporadic ALS patients.