Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of-function may be an enhanced ability of the mutant SOD1 to generate .OH radicals or to facilitate peroxynitrite-mediated nitration of proteins. We found significant increases in concentrations of 3-nitrotyrosine, a marker of peroxynitrite-mediated nitration, in upper and lower spinal cord and in cerebral cortex of transgenic mice with the FALS-associated G93A mutation. Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration.
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PMID:Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. 930 54

The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.
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PMID:Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. 1007 62

There is a large body of evidence implicating oxidative damage in the pathogenesis of both normal aging and neurodegenerative diseases. Oxidative damage to proteins has been well established. Although there are a large number of potential oxidative modifications only a few have been systematically studied. The most frequently studied marker of oxidative damage to proteins is protein carbonyl groups. 3-Nitrotyrosine is thought to be a relatively specific marker of oxidative damage mediated by peroxynitrite. Increased concentrations of both protein carbonyls and 3-nitrotyrosine have been documented in both normal aging as well as in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These findings help to provide a rationale for trials of antioxidants in neurodegenerative diseases.
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PMID:Oxidatively modified proteins in aging and disease. 1197 81

3-Nitrotyrosine (3-NT) is used as a biomarker of nitrosative stress. The formation of 3-NT has been reported in a number of diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and cancer. The nitration of proteins is a reversible process, but it can induce a conformational change and thereby functional alterations of the affected protein. 3-NT measurements in biological samples are usually carried out by methodologies such as immunohistochemistry, high-performance liquid chromatography, gas chromatography, and immunochemical detection. This chapter describes the immunochemical method for the determination of protein-bound 3-NT using slot-blot analysis.
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PMID:Slot-blot analysis of 3-nitrotyrosine-modified brain proteins. 1842 27

Reactive oxygen species are generated as a by-product of routine biochemical reactions. However, dysfunction of the antioxidant system or mutations in gene function may result in the elevated production of the pro-oxidant species. Modified endogenous molecules due to chemical interactions with increased levels of reactive oxygen and nitrogen species in the cellular microenvironment can be termed as biomarkers of oxidative stress. 3-Nitrotyrosine is one such promising biomarker of oxidative stress formed due to nitration of protein-bound and free tyrosine residues by reactive peroxynitrite molecules. Nitration of proteins at the subcellular level results in conformational alterations that damage the cytoskeleton and result in neurodegeneration. In this review, we summarized the role of oxidative/nitrosative processes as a contributing factor for progressive neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease and Prion disease. The selective tyrosine protein nitration of the major marker proteins in related pathologies has been discussed. The alteration in 3-Nitrotyrosine profile occurs well before any symptoms appear and can be considered as a potential target for early diagnosis of neurodegenerative diseases. Furthermore, the reduction in 3-Nitrotyrosine levels in response to treatment with neuroprotective has been highlighted which is indicative of the importance of this particular marker in oxidative stress-related brain and central nervous system pathologies.
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PMID:3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases. 3191 43