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)

Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use.
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PMID:Reactive oxygen species and the central nervous system. 140 8

Down's Syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of the chromosome numbered 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain where the occurrence of Alzheimer's disease (AD) is observed in all trisomy 21 patients over the age of 35. Elucidation of the biological mechanisms leading to brain aging in DS might provide new insight into the understanding of brain aging and AD in normal people. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all DS tissues. The level of CuZnSOD protein and mRNA is particularly high in hippocampal pyramidal neurons susceptible to degenerative processes in AD and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. Increased CuZnSOD activity in these age-related neurodegenerative disorders might result in H2O2 overproduction and subsequently promote peroxidative damages within cells. Increase of seleno-dependent glutathione peroxidase (Se-GPx) in DS cells supports this concept. In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed. In cells transfected with the human CuZnSOD gene, and increased Se-GPx activity is observed, a situation which mimics DS. In mice transgenic for the human CuZnSOD, the expression pattern of the transgene in the brain is similar to that in humans, and we can observe an increased peroxidation in this tissue. These data, like others in the literature, support the hypothesis that excess CuZnSOD induces an imbalance in the regulation of oxygen-derived free radical production which might result in peroxidative brain damage and possibly contribute to accelerated aging and age-related neuropathology.
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PMID:Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: models for the study of free radical metabolism and aging. 145 Jun 8

Several recent studies have shown decreased copper and increased zinc concentrations in the substantia nigra and increased copper concentrations in the cerebrospinal fluid of Parkinson's disease patients. To elucidate whether changes in serum levels of these trace elements may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of zinc and copper by flame atomic absorption spectrophotometry, and albumin and ceruloplasmin, in 32 (Zn) and 39 PD patients (Cu), respectively, with their spouses as the control group. Serum zinc, albumin, copper and ceruloplasmin levels and the zinc/albumin and copper/ceruloplasmin ratios, did not differ significantly between the two groups and were not influenced by antiparkinsonian therapy in the PD patients. Serum zinc/albumin ratio (r = 0.43), ceruloplasmin (r = -0.36) and copper/ceruloplasmin ratio (r = 0.36) correlated significantly with age, but not with age of onset, duration of the disease, scores of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging in PD patients. These values did not correlate with age in the control group. These results suggest that serum levels of zinc and copper do not play any role as risk factors for PD.
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PMID:Serum levels of zinc and copper in patients with Parkinson's disease. 146 36

Nutritional status was assessed in a group of patients with Parkinson's disease. Weight loss since the onset of disease occurred in 52% of the patients and 22% had lost more than 12.8 kg. Although 67% of patients experienced eating difficulties of some kind, dietary intakes of protein and energy were not significantly lower than recommended intakes. Plasma levels of albumin (44.2 g/l vs 45.7 g/l), vitamin A (2.61 vs 2.94 mumol/l), vitamin E (22.0 vs 32.0 mumol/l), iron (15.3 vs 18.3 mumol/l) and zinc (14.2 vs 18.7 mumol/l) were significantly lower (P < 0.05) in the patients than in healthy controls. Levels of ferritin, total iron-binding capacity and copper were similar between groups. The potential significance of low levels of vitamin E and zinc are discussed in relation to oxidative stress in the pathogenesis of this disease.
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PMID:Diet, body size and micronutrient status in Parkinson's disease. 148 17

Previously we have shown that cell death in the substantia nigra (SN) in Parkinson's disease (PD) is associated with an increase in iron content but a decrease in the level of the iron-binding protein ferritin. Alterations in other metal ion levels were also observed; copper levels were reduced, whereas zinc levels were increased. The importance of these changes in iron, ferritin, and other metal ions in the pathophysiology of PD depends on whether they are specific to the illness. We measured levels of iron, copper, zinc, manganese, and ferritin in postmortem tissue from patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) (which shows pathology in the SN and striatum) and Huntington's disease (HD) (which shows pathological changes in the striatum, compared with control subjects). Total iron levels were elevated in areas of the basal ganglia showing pathological changes in these disorders. In particular, total iron content was increased in SN in PD, PSP, and MSA, but not in HD. Total iron levels in the striatum (caudate nucleus and/or putamen) were increased in PSP, MSA, and HD, but not in PD. There were no consistent alterations in manganese levels in the basal ganglia in any of the diseases studied. Copper levels were decreased in the SN in PD and in the cerebellum in PSP, and were elevated in the putamen and possibly the SN in HD. Zinc levels were only increased in PD in the SN, the caudate nucleus, and the putamen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia. The Royal Kings and Queens Parkinson's Disease Research Group. 151 Mar 87

To elicit possible variations in the CSF concentrations of copper, iron and manganese due to Parkinson disease (PD) or to the stage reached, we tested 11 patients with idiopathic PD, 6 untreated and 5 on long term L-dopa, versus 22 age and sex matched patients with other neurological disorders (control group-CG). The CSF levels of the three metals, measured by electrothermal atomization, did not differ significantly between the PD group and CG or between either of the PD subgroups and CG. Our findings therefore do not support the hypothesis that CSF Cu is a marker of PD.
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PMID:A case control study of CSF copper, iron and manganese in Parkinson disease. 162 80

Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors.
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PMID:Iron in brain function and dysfunction with emphasis on Parkinson's disease. 164 57

Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self-administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study.
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PMID:A pilot study of occupational and environmental risk factors for Parkinson's disease. 174 30

Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.
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PMID:Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. 183 73

The contents of indispensable major elements sodium (Na), phosphorus (P), calcium (Ca), magnesium (Mg), trace elements iron (Fe), copper (Cu), nickel (Ni), zinc (Zn), strontium (Sr), vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), and other elements lead (Pb), silicon (Si), aluminium (Al), titanium (Ti), barium (Ba), lanthanum (La), cadmium (Yb), cerium (Ce), scandium (Sc), silver (Ag), in cerebrospinal fluid (CSF) were measured in 13 patients suffering from Parkinson disease before and after autotransplantation of adrenal medulla. It was found that while the patients' objective symptoms were relieved and the contents of monoamine transmitters were changed, the contents of P, V, Co, Cr, in CSF increased significantly (P less than 0.05 or 0.01) at the first, 2nd, 4th, 6th, and 8th week, the contents of Mn in CSF also increased significantly at the first 4th week (P less than 0.05) but decreased significantly at the 8th week the contents of Zn in CSF increased significantly (P less than 0.05) at the 2nd week; Mo increased significantly (P less than 0.05 or 0.01) at the 4th and 8th week B increased significantly (P less than 0.05) at the first week; the contents of Ca, Na, Sr, Ba, Al, Ti, La, Ce, Yb, Sc, Ag in CSF increased significantly (P less than 0.05 or 0.01) at the 8th week, Mg, Fe, Cu Ni, Pb, Si, Cd remained unchanged after operation. The results suggest that the contents of these chemical elements can be affected by this kind of operation, indicating that these elements are involved in the pathogenesis of Parkinsonism.
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PMID:[Determination of multiple chemical elements in CSF in Parkinson disease after intracerebral autotransplantation of the adrenal medulla]. 186 88


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