Biopolymers and cell. 1997; 13 (6): 513 - 515

Oxidative stress and neurodegenerative disorders

/. 5. Magura, O. M. Rozhmanova

The reduction of molecular oxigen to water during the course of oxidative-phosphorylation involves the formation of superoxide radical (O2 ), hydrogen peroxide (H2O2), and hydrox.il radical (HO'), known collectively as reactive oxidant species (ROS). Neurons are particularly vulnerable to H2O2. Transition metals such as iron interact with H2Oj to form the highly destructive OH radical. The hydroxil radical is a particularly reactive oxidizing agent and is thought to be the prime mediator of oxigen toxicity. ROS can destabilize cellular calcium homeostasis by damaging mitochondrial electron transport, resulting in ATP depletion, which, in turn, compromises ion-motive ATPases. The maintenance of mitochondrial function may be a decisive factor in determining the degree and progression of neuronal injury caused by excitotoxins. ROS can also directly damage membrane ion pumps and channels. ROS contribute to the pathogenesis of some neurodegenerative disorders. The glutamate toxwity involves peroxide production, which contributes to loss of Ca * homeostasis. Neurotrophic factors attenuate glutamgte-induced accumulation of peroxides, elevation of intraceilular Ca concentration, neuroioxicity and increase anti oxidant enzyme activities in neurons. Accumulating evidence indi¬cates that excessive formation of free radicals may be involved in the pathophysiology of many neurodegenerative diseases, including Alzlieimer's disease, Partition's disease, Huntington's disease and amyotrophic lateral sclerosis. Oxidative stress is also implicated in acute brain disorders such as ischemia and traumatic damage.