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)

The primary pathological change in Parkinson's disease is the destruction of dopamine containing cells in the zona compacta of substantia nigra. The cause of nigral cell death and the underlying mechanism remains elusive. However, the discovery of the selective nigral neurotoxin MPTP and its ability to inhibit mitochondrial energy metabolism via its metabolite MPP+ and to generate superoxide radicals suggests processes by which nigral cell death might occur. Recent postmortem evidence in brain tissue from patients dying with Parkinson's disease also suggests the occurrence of some on-going toxic mechanism. This may be a free radical process stimulated by an excess of iron within substantia nigra coupled to a generalised decrease in brain ferritin content. These data suggest altered iron handling occurs in Parkinson's disease which may lead to the generation of toxic oxygen species such as superoxide radicals. There is also evidence for an inhibition of mitochondrial function in the substantia nigra in patients with Parkinson's disease. So there may be a close association between the actions of the synthetic neurotoxin MPTP and the underlying cause of idiopathic Parkinson's disease.
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PMID:Clues to the mechanism underlying dopamine cell death in Parkinson's disease. 266 76

High-field strength magnetic resonance imaging is an accurate clinical technique for detecting the relative distribution of ferritin in the brain. In normal adults, iron is found in highest concentrations in the globus pallidus, red nucleus, pars reticulata of the substantia nigra, and dentate nucleus of the cerebellum; its distribution is clearly mapped as signal hypointensity (darkness) on a T2-weighted image due to local-field heterogeneities produced by ferritin. Iron is absent at birth and increases in concentration in the putamen in the elderly. Poorly drug-responsive Parkinson's disease (multiple-system atrophy) is characterized by premature signal hypointensity in the putamen and caudate, while Hallervorden-Spatz disease exhibits abnormal hypointensity in the globus pallidus in children. Dyskinetic disorders often have abnormal signal hyperintensity (whiteness) in the putamen related to gliosis.
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PMID:Magnetic resonance imaging and extrapyramidal movement disorders. 271 6

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

Although iron accumulates in the brain in a number of pathological conditions, including Hallervorden-Spatz syndrome, Parkinson's disease, and neurosyphilis, studies of brain iron metabolism have been performed only rarely. Neuronal-enriched cultures were prepared from fetal mouse brain. After 18 days the cells were exposed to radiolabeled iron. Total iron uptake and incorporation into ferritin were rapid and linear over four hours. The addition of either methylamine or ammonium chloride, both known blockers of transferrin-iron release through their lysosomotropic properties, inhibited total iron uptake. Methylamine also inhibited the rate of ferritin-iron incorporation, most likely by interfering with transferrin-iron release. The data suggest that neuronal iron transport, much like that in other mammalian tissues, is transferrin mediated and that blockers of transferrin-iron release may be of value in conditions in which there is brain iron overload.
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PMID:Iron uptake by mammalian cortical neurons. 646 62

Iron is the most abundant metal in the human body (Pollitt and Leibel, 1982; Youdim, 1988), and the brain, like the liver, contains a substantially higher concentration of iron than of any other metal (Yehuda and Youdim, 1988). Within the brain, iron shows an uneven distribution, with high levels in the basal ganglia (substantia nigra, putamen, caudate nucleus, and globus pallidus), red nucleus, and dentate nucleus (Spatz, 1922; Hallgren and Sourander, 1958; Hill and Switzer, 1984; Riederer et al., 1989). Iron deposition in the brain is mainly in organic storage forms such as ferritin but not hemosiderin (Hallgren and Sourander, 1958; Octave et al., 1983), with relatively little in a free and reactive form. Although the function of a regionally high brain iron content is unknown, the homeostasis of brain iron is thought to be necessary for normal brain function, especially in learning and memory (Youdim et al., 1989; Yehuda and Youdim, 1989; Pollit and Metallinos-Katsaras, 1990; Youdim, 1990). Thus, a high content of brain iron may be essential, particularly during development, but its presence means that injury to brain cells may release iron ions that can lead to oxidative stress via formation of oxygen free radicals. Such radicals are thought to be involved in lipid peroxidation of the cell membrane, leading to increased membrane fluidity, disturbance of calcium homeostasis, and finally cell death (Youdim et al., 1989; Halliwell, 1992). Iron is an essential participant in many metabolic processes, including (a) DNA, RNA, and protein synthesis, (b) as a cofactor of many heme and nonheme enzymes, (c) the formation of myelin, and (d) the development of the neuronal dendritic tree (Ben-Shachar et al., 1986; Youdim et al., 1991b). A deficiency of iron metabolism would therefore be expected to alter some or all of these processes (Jacobs and Worwood, 1980; Youdim, 1985, 1988). Studies of iron distribution in the human brain have demonstrated that the degree of iron deposition, primarily in the basal ganglia (a predominantly dopamine structure), increases with age (Hallgren and Sourander, 1958) and in certain disorders, most notably the basal ganglia disorders (Seitelberger, 1964). This review will present some of the experimental evidence indicating a role of disturbed iron metabolism as a cause of the neurodegenerative disorder Parkinson's disease and possibly other neurodegenerative disorders such as Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered brain metabolism of iron as a cause of neurodegenerative diseases? 751 59

An anti-tau monoclonal antibody tau-2 was demonstrated to react with the cells which characteristically appeared in the subcortical nuclei of certain neurodegenerative disorders. These cells had rod-like cell bodies and elongated processes, whose morphology was consistent with that of reactive microglia (tau-2 positive microglia-like cells; TPMC). TPMC were diffusely scattered in the subcortical nuclei, especially the putamen, irrelevant to focal tissue injury such as infarcts and amyloid deposits. TPMC were positively immunostained with anti-ferritin antibody, but negatively with LN3, anti-GFAP, other kinds of anti-tau and anti-neurofilament antibodies. TPMC were found in some cases of Alzheimer type dementia and diffuse Lewy body disease, but not in the cases of Parkinson's disease, Pick's disease and control without neurological disorder. Similar microglia-like cells were found around infarctic foci and amyloid cores of senile plaques, regardless of the disorder. They were, however, different from TPMC in that they were positively immunostained with LN3.
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PMID:Investigation of tau-2 positive microglia-like cells in the subcortical nuclei of human neurodegenerative disorders. 756 36

Ferritin contains the greatest part of the iron found in the brain, and the release of iron stores from ferritin has an essential role in iron-dependent lipid peroxidation. We examined the effect of cultured microglia on iron mobilization from ferritin. Microglia stimulated by phorbol myristate acetate caused the release of iron from ferritin, which was detected by monitoring iron-ferrozine complex formation. This iron mobilization was mediated by microglial superoxide production, as evidenced by the significant inhibitory effect of superoxide dismutase. The role of superoxide was also supported by the close correspondence of cumulative microglial superoxide production, as demonstrated by the MCLA (Cypridina luciferin analogue)-dependent chemiluminescence assay, to the time course of iron release from ferritin. Iron release induced by activated microglia may be partly responsible for the oxidative damage that is thought to occur in Parkinson's disease and other neurodegenerative disorders.
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PMID:Activated microglia cause superoxide-mediated release of iron from ferritin. 762 46

Iron is believed to play a role in the pathogenesis of both Parkinson's disease (PD) and Alzheimer's disease (AD). We measured ferritin, which is considered to be the iron storage protein, in CSF of patients with PD, AD, and multiple system atrophy (MSA) as well as control subjects. We found a significant increase in CSF ferritin in AD compared with both PD and age-matched controls. No significant differences were found between PD patients with dementia (PDD) and non-demented PD patients. For non-demented PD patients a positive correlation between CSF ferritin and age was found. Our results may indicate that iron has a role in the pathophysiology of AD.
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PMID:Cerebrospinal fluid ferritin levels of patients with Parkinson's disease, Alzheimer's disease, and multiple system atrophy. 771 Jun 63

To elucidate the possible role of peripheral metabolism of iron in the risk for developing Parkinson's disease (PD), we compared serum levels of iron, transferrin and ferritin, and 24-h iron excretion in urine after a single intramuscular dose of 1 mg/kg desferrioxamine, in 68 PD patients and their spouses as the control group. All these values did not differ significantly between the groups, they were not influenced by antiparkinsonian therapy, and they did not correlate with age, age at onset and duration of the disease, scores of the Unified PD Rating Scale or the Hoehn and Yahr staging in the PD group, with the exception of the 24-h urinary iron excretion with the duration of the disease (r = 0.32, p < 0.05). These results suggest that peripheral metabolism of iron is apparently unrelated to the risk of developing PD.
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PMID:Peripheral iron metabolism in patients with Parkinson's disease. 796 93

Elevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron-ferritin ratio and complex I activity in the substantia nigra samples.
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PMID:Complex I, iron, and ferritin in Parkinson's disease substantia nigra. 799 74


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