Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this article is to emphasize the important role that copper plays in the function of nerve cells. We are reporting preliminary data which suggest that the swelling of axons which we produce in rats by iminodipropionitrile, IDPN, is due to its chelating action on copper, and how conversely supplementation with copper abolishes both symptoms and lesions. The copper values we obtained by atomic absorption spectrophotometry of the spinal cord and brain from the animals fully support this contention. In comparing these results with the diseases that are known to be due to copper deficiency, namely Menkes disease in man, swayback in lambs and several neurological mutant mice, we find not only similar axonal swellings, but also amelioration of symptoms and lesions by early administration of copper. Considering the main forms in which copper is present, we discuss the cuproproteins, i.e. ceruloplasmin and metallothionein, and their role in transport and delivery of copper to various organs. Further, the many cuproenzymes i.e. superoxide dismutase, tryptophan-2,3-dioxygenase, lysine oxidase, cytochrome oxidase, monoamine oxidases, tyrosinase, dopamine-beta-hydroxylase and d-amino levulinate dehydratase are noted for their roles in the nervous system. Finally, we suggest that neuronal copper deficiency should be more fully investigated as a possible etiological factor in the more common neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, ALS.
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PMID:Deficiency of copper can cause neuronal degeneration. 161 61

Sporadic Amyotrophic Lateral Sclerosis (SALS) is a fatal neurologic disease characterized by degeneration of motor neurons in the spinal cord, brainstem and cortex. While familial cases of ALS exist, the sporadic form accounts for the majority of adult-onset cases. It has been hypothesized that the neurodegenerative mechanisms underlying SALS might arise from glutamate-mediated excitotoxicity and mitochondrial dysfunction. Studies on autopsied SALS spinal cord and brain have reported decreased cytochrome oxidase activity, decreased astrocytic glutamate-transporter protein, and alterations of glutamate levels and glutamate metabolizing enzyme activities. We conjectured that if alterations in glutamate metabolism and cytochrome oxidase activity occur in the SALS central nervous system these alterations may also be manifested in peripheral tissues such as platelets in living SALS patients. In this study we compared the activities of cytochrome oxidase, citrate synthase, glutamate dehydrogenase and glutaminase in platelets from SALS and control subjects. We found that there were no differences in any of the enzyme activities measured between the two groups. Our data argue against generalized ubiquitous biochemical alterations of these enzymes in SALS patients.
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PMID:Unaltered cytochrome oxidase, glutamate dehydrogenase and glutaminase activities in platelets from patients with sporadic amyotrophic lateral sclerosis--a study of potential pathogenetic mechanisms in neurodegenerative diseases. 1145 96

Mitochondrial dysfunction and abnormal electron chain transport (ECT) may be involved in the pathogenesis of ALS. The aim of this study was to investigate the effect of cerebrospinal fluid (CSF) from ALS patients on the activity of ECT enzymes in mitochondrial cerebral crude preparations in the rats. We found that CSF inhibited the activity of complex I-III in 20%, complex II-III in 12% and complex IV in 33% of the ALS patients. CSF from the controls did not affect the activity of complex I-III and II-III. The effect of the CSF ultrafiltrates with cut off below 5000 daltons on the activity of ECT enzymes was also investigated. The CSF ultrafiltrates inhibited the activity of complex I-III, complex II-III and complex IV in 38%, 44% and 53% of the ALS patients, and in 80%, 53% and 43% of the controls, respectively. The results of this study and our previously reported experiments on the sera of ALS patients may indicate that neurotoxic effects of body fluids from ALS patients could be mediated by inhibition of the respiratory chain enzymes. This confirms an important role of mitochondrial dysfunction in the pathogenesis of ALS.
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PMID:[The role of mitochondrial respiratory chain in the pathogenesis of ALS]. 1173 84

It has been shown that chronic treatment with lithium carbonate (Li(2)CO(3)) in presymptomatic SOD1G93A transgenic male mice, a model of ALS, was able to remarkably increase their lifespan through the activation of autophagy and the promotion of mitochondriogenesis and neurogenesis. This prompted us to test the lithium effect also in female SOD1G93A mice with two phenotypes of different disease severity. Female SOD1G93A mice of C57BL/6J or 129S2/Sv genetic background were treated daily with Li(2)CO(3) 37 mg/kg (1 mEq/kg) i.p. starting from age 75 days until death. Grip strength, latency to fall on rotarod and body weight were monitored twice weekly. At the time of death the spinal cord was removed to assess the number of motor neurons and to measure the expression of a marker of autophagy (LCII) and the activity of mitochondrial complex IV. We observed a significant anticipation of the onset and reduced survival in 129Sv/G93A and no effect in C57/G93A mice treated with lithium compared to vehicle treated mice. Moreover, lithium neither exerted neuroprotective effects nor increased the expression of LCII and the activity of mitochondrial complex IV in the spinal cord. The present study does not identify any therapeutic or neuroprotective effect of lithium in SOD1G93A female mice.
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PMID:Treatment with lithium carbonate does not improve disease progression in two different strains of SOD1 mutant mice. 1930 67