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)

We examined the cytotoxicity of dopa and dopamine for cultured neurons by using a newly developed enzyme immunoassay for neurofilament protein to determine surviving neuronal numbers. Each of the two catechols caused neuronal death in the presence of iron with or without superoxide dismutase and catalase, while deferoxamine mesylate prevented neuronal loss. Lipid peroxidation of phospholipid liposomes was confirmed to be produced by the combination of the catechols and iron (Fe3(+)-ADP complex). Thus, it was strongly suggested that cultured neurons were killed via the peroxidative cleavage of cell membrane components provoked by the catechols and iron. This mechanism of neuronal loss may play an important role in the degeneration in the substantia nigra of Parkinson's disease, because the catechols and iron are abundant in this region.
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PMID:Dopa and dopamine cause cultured neuronal death in the presence of iron. 190 38

As an animal model of human Parkinson's disease 250 micrograms of 6-Hydroxydopamine was injected intraventricularly in the rats. At 24 h, 48 h, 7th and 14th day after injection, the levels of dopamine, norepinephrine, Cu, Zn- and Mn- superoxide dismutase (SOD), catalase as well as the lipid peroxidative products in the striatum, midbrain and hypothalamus were determined. Our data showed that catecholamines decreased persistently, catalase and Mn-SOD decreased concomitantly, Cu, Zn-SOD, however, remained, unchanged. Lipid peroxidative products increased shortly after injection, then subsided. Our result suggests that lipid peroxidation might be involved in the degenerative process of neurons in Parkinson's disease.
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PMID:[Effect of 6-hydroxydopamine on cerebral catecholamines, lipid peroxidation and antioxidant enzymes in rats-concerned with pathogenesis of Parkinson's disease]. 195 95

The involvement of oxygen radicals in the pathogenesis of Parkinson's disease has been suggested for some time. This article reviews the evidence supporting the involvement of oxygen radicals in the disease process in the brain. This includes a discussion of iron, lipid peroxidation, peroxidase, catalase, superoxide dismutase, and glutathione levels in the brain. In addition, various theories of induction of Parkinson's disease are discussed in relation to the possible involvement of oxygen radicals. These theories include the environmental toxin theory, the dopamine turnover theory, and the cerebral blood flow theory.
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PMID:Oxygen free radicals and Parkinson's disease. 201 74

Although many authors have suggested that dopamine and its metabolites producing free radicals have an harmful effect in the substantia nigra, experimental evidence has not been shown. Using a newly established enzyme immunoassay of the neurofilament protein, a reliable index for the number of survived neurons in tissue culture, we evaluate the effects of Dopa on the neurons of dorsal root ganglia from mice. Neurons were destroyed by the exposure of 0.5 mM Dopa with or without superoxide dismutase and catalase, but they were saved by the pretreatment with 1.0 mM deferoxamine mesylate, a powerful iron-chelating agent. Formation of malondialdehyde, an index of lipid peroxidation, was also observed in the reaction of 0.5 mM Dopa and cerebral cortical neurons from new-born rats only when iron was present. These results indicate that Dopa initiates lipid peroxidation of cell membrane in the presence of a small amount of iron in the culture with little or no participation of reactive oxygen species, leading to the destruction of the neurons. In Parkinson's disease, the cytotoxic mechanism of Dopa and iron may involve the neuronal degeneration in the substantia nigra abundant in iron and dopaminergic neurons.
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PMID:[Iron-dependent cytotoxic effects of dopa on cultured neurons of the dorsal root ganglia]. 211 13

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

Oxygen-derived toxicity has been suggested as being involved in the pathogenesis of Parkinson's disease. Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase provide the enzymatic defence against oxygen toxicity. The activities of these enzymes were measured in peripheral blood leucocytes, cerebrospinal fluid and in different brain regions from patients with idiopathic Parkinson's disease and from controls. There was no indication of a generalized defect in any of these enzymes in Parkinson's disease. The brain activities of catalase, glutathione peroxidase and glutathione reductase were also comparable to those of the controls. An increased superoxide dismutase-like activity was observed in several regions of parkinsonian brains, including the temporal cortex, thalamus and red nucleus. However, the most pronounced increase occurred in the substantia nigra and basal nucleus. This may be due to an increase of the superoxide dismutase activity or be a result of the presence of a compound with superoxide dismutase-like activity, and may reflect the involvement of radical-induced cell damage in the pathogenesis of Parkinson's disease.
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PMID:Oxygen toxicity protecting enzymes in Parkinson's disease. Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. 322 Dec 44

Recent evidence suggests that among the factors that lead to neurodegenerative changes in Parkinson's disease are stimulation of lipid peroxidation and deficiency of glutathione and glutathione peroxidase in substantia nigra. We have investigated the effect of neurodegenerative changes on plasma and erythrocytes of patients with Parkinson's disease and compared the results with those of age-matched controls. Both plasma lipid peroxide levels and erythrocyte susceptibility to lipid peroxidation were significantly increased in Parkinson's disease. Erythrocyte fragility tests revealed that in 35% of the patients there was increased fragility. In addition, erythrocyte catalase activities were not changed whereas glutathione levels and glutathione peroxidase activities were decreased in Parkinson's disease. Our results suggest that erythrocyte membrane integrity may be impaired in Parkinson's disease.
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PMID:Increased erythrocyte susceptibility to lipid peroxidation in human Parkinson's disease. 338 Mar 50

Three groups have reported defective antioxidant mechanisms in substantia nigra of patients with Parkinson's disease, namely a decreased catalase and peroxidase activity, a reduction of glutathione and, more recently, a diminished nigral glutathione peroxidase activity. We decided to investigate these mechanisms in erythrocytes to determine whether these brain defects represent generalized or genetic aberrations, in which case they should also be present in blood cells. The glutathione cycle has been investigated (reduced and oxidized glutathione, glutathione reductase and peroxidase) plus the activities of catalase and superoxide dismutase. The basal malonaldehyde content of erythrocytes was used as an index of endogenous lipid peroxidation. None of the above-mentioned parameters were found altered in erythrocytes of parkinsonians, suggesting that no genetic or generalized biochemical abnormalities underly the deficiencies detected in substantia nigra.
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PMID:Erythrocyte antioxidant activity in human patients with Parkinson's disease. 358 38

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

Two psychiatric screening instruments, the Mini-Mental State (MMS), a test for cognitive disturbance, and the General Health Questionnaire (GHQ), were administered to 197 neurological in-patients. The results suggest a high rate of psychiatric disturbance. The highest rate of cognitive disturbance detected by the MMS was found in patients with Parkinson's disease. The highest rates of emotional disturbance indicated by GHQ scores were related to myasthenia gravis and multiple sclerosis. MMS scores but not GHQ scores were related to standard tests of cognition, the diagnosis of cerebral pathology, and CAT scan abnormality. The results also demonstrate that the GHQ does not adequately detect patients with cognitive impairment. It is concluded that in populations at high risk for cognitive impairment a tandem screening procedure utilizing tests for both cognitive and emotional disorders is needed.
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PMID:Psychiatric screening on a neurological ward. 738 13


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