Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduced and oxidized glutathione concentrations in post-mortem brain tissue from the substantia nigra of control subjects and patients with neuropathologically confirmed Parkinson's disease were measured by a coulometric method using high-pressure liquid chromatography and electrochemical detection. Reduced glutathione concentrations were decreased in the substantia nigra of parkinsonian patients compared with controls. Differences in the concentration of oxidized glutathione and in the percentage of oxidized glutathione of the total glutathione were not observed between parkinsonian and control subjects. The finding that oxidized glutathione is not decreased in Parkinson's disease suggests that the decrease in reduced glutathione is not exclusively the consequence of neuronal loss in the substantia nigra but may indicate a state of oxidative stress.
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PMID:Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. 145 5

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8 micrograms/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 micrograms/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 micrograms/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.
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PMID:Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. 195 64

The degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson's disease (PD). However, the etiology of this degeneration is not known. Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease. An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper. The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN). Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD.
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PMID:Oxidative stress: a role in the pathogenesis of Parkinson's disease. 219 8

The recent studies on the chemical pathology of Parkinson's disease show selective increases of iron and lipid peroxidation and decreased glutathione (GSH) oxidizing capacity in the substantia nigra (SN). These changes are indicative of oxidative stress, possibly due to the accumulation of iron in the SN. It is the melaninized dopamine neurons that are vunerable to degeneration. The investigation of the interaction of iron with dopamine melanin demonstrates the presence of two relatively high affinity binding sites for 59Fe3+ on dopamine melanin. Interaction of Fe3+ with dopamine melanin results in potentiation of lipid peroxidation of rat cerebral cortex as compared to that induced by Fe3+. Only compounds with the ability to chelate iron are able to inhibit the binding of Fe3+ to melanin and the resultant lipid peroxidation. Therapeutic use of iron chelators, with the ability of crossing the blood brain barrier, as agents for retarding the oxidative stress and Parkinson's disease is envisaged.
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PMID:Selectivity of melaninized nigra-striatal dopamine neurons to degeneration in Parkinson's disease may depend on iron-melanin interaction. 219 9

The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients. Although marked regional distributions of iron, magnesium, and calcium were present, there were no changes in magnesium, calcium, and copper in various brain areas of PD. The most notable finding was a shift in the iron (II)/iron (III) ratio in favor of iron (III) in substantia nigra and a significant increase in the iron (III)-binding, protein, ferritin. A significantly lower glutathione content was present in pooled samples of putamen, globus pallidus, substantia nigra, nucleus basalis of Meynert, amygdaloid nucleus, and frontal cortex of PD brains with severe damage to substantia nigra, whereas no significant changes were observed in clinicopathologically mild forms of PD. In all these regions, except the amygdaloid nucleus, ascorbic acid was not decreased. Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron (III) suggest that these changes might contribute to pathophysiological processes underlying PD.
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PMID:Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. 291 Oct 28

We measured amino acid contents in autopsied brains of seven patients with progressive supranuclear palsy (PSP) and in control subjects dying without brain disease. Glutathione was also quantitated in rapidly frozen brains of PSP patients, Parkinson's disease (PD) patients, and controls. In PSP, we found glutamic acid markedly increased in the nucleus accumbens; taurine significantly increased in nucleus accumbens, substantia nigra, and globus pallidus; and gamma-aminobutyric acid significantly increased in nucleus accumbens and putamen. Glycerophosphoethanolamine contents were significantly increased in most regions. Glutathione, which is significantly decreased in substantia nigra in PD, was increased in this brain region in PSP, suggesting that different mechanisms may be responsible for destruction of dopaminergic nigrostriatal neurons in these two disorders.
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PMID:Brain amino acids and glutathione in progressive supranuclear palsy. 336 77

The present communication surveys the present knowledge about the extent to which formation of free radicals in the central nervous system may give rise to cross-linking reactions finally ending in the deposition of lipofuscin pigments. Free radicals may be formed by autoperoxidation of polyunsaturated fatty acids. These fatty acids, e.g., C22:6 omega 3, are enriched in rods and cones of the eye and in phosphatidyl ethanolamine of synaptosomes. By peroxidation, malondialdehyde is formed. This aldehyde may cross-link through amino groups of proteins and certain phospholipids. Hereby, lipofuscin is deposited. The peroxidation process is counteracted by certain enzymic systems and by antioxidants. Thus, glutathionperoxidase (GSH-Px), catalase and superoxid dismutase may eliminate peroxides. GSH-Px is a selenium-containing enzyme. Peroxides are also formed by metabolic transformation of dopamine. 3 demential syndromes, i.e. Alzheimer's, Parkinson's and Batten's diseases, are discussed with regard to whether the "free radical theory" may explain the pathogenesis. Finally, it is discussed whether an antioxidative treatment including vitamins E and C as well as a supplement of selenium, e.g. sodiumselenite, may be a therapeutic alternative to other types of treatment of demential syndromes or a direct supplement to the L-DOPA treatment of Parkinson's disease.
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PMID:Demential syndromes and the lipid metabolism. 650 44

Amino acid analysis of autopsied human brain showed reduced glutathione (GSH) content significantly lower in the substantia nigra than in other brain regions. GSH was virtually absent in the nigra of patients with Parkinson's disease. Oxidative degradation of L-DOPA and dopamine in vivo may generate reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical, or singlet oxygen) which can damage membranes and other cellular components. Since GSH is an important natural antioxidant, a deficiency of GSH in the substantia nigra could make this region vulnerable to oxidative injury. If confirmed, the hypothesis that loss of nigrostriatal dopaminergic neurons results from a regional GSH deficiency could have important therapeutic implications for the management and prevention of Parkinson's disease.
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PMID:Parkinson's disease: a disorder due to nigral glutathione deficiency? 716 92

The mechanism of nigral cell death in Parkinson's disease (PD) remains unknown, but it is increasingly proposed that free radical reactions are important in the disease pathology. One of the most striking features of PD is an approximate 40% decrease in the levels of reduced glutathione (GSH) which occurs early in the development of the disease. We describe a possible mechanism of GSH depletion which results from the reaction of L-DOPA and dopamine with the superoxide free radical (O2.-) and leads to a very rapid loss of GSH.
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PMID:Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinson's disease. 757 29

Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). However, it is unclear if altered antioxidant enzyme activity is sufficient to increase lipid peroxidation in PD. We therefore investigated if MPTP can alter the activity of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) and the level of lipid peroxidation. L-Deprenyl, prior to MPTP administration, is used to inhibit MPP+ formation and its subsequent effect on antioxidant enzymes. MPTP induced a threefold increase in SOD activity in the striatum of C57BL/6 mice. No parallel increase in GSH-PX or CAT activities was observed, while striatal lipid peroxidation decreased. At the level of the substantia nigra (SN), even though increases in CAT activity and reduction in SOD and GSH-PX activities were detected, lipid peroxidation was not altered. Interestingly, L-deprenyl induced similar changes in antioxidant enzymes and lipid peroxidation levels, as did MPTP. Taken together, these results suggest that an alteration in SOD activity, without compensatory increases in CAT or GSH-PX activities, is not sufficient to induce lipid peroxidation.
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PMID:Effect of MPTP and L-deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain. 759 71


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