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)

Iron dysregulation in the brain is thought to contribute to the oxidative damage seen in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. A role for iron in the oxidative stress thought to contribute to normal ageing is less certain. To better characterize the role of iron in normal ageing, the concentrations of iron, transferrin, ferritin, and protein carbonyl groups are measured in nine separate regions of Fischer 344 rats. The largest (approximately 30%) age-related increases in brain iron concentration are seen in the temporal cortex, medial septum, and cerebellum. Ferritin concentration in these same brain regions increases 50 to 250% with age, while protein carbonyl concentration is only -27 to +4%, of young rats. These results indicate that an increase in the major iron-binding protein ferritin compensates for any age-related increase in iron concentration, and suggest that the increased ferritin is cytoprotective, serving to prevent the accumulation of protein carbonyl groups (a principal product of metal-catalysed oxidation of proteins).
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PMID:Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains. 917 81

Iron deposition in the substantia nigra in Parkinson's disease has been associated with an increase in lactoferrin receptors and a reduction in ferritin concentration. This accumulation of iron in the brain may accelerate free radical formation, lipid peroxidation, and neuronal death. Remarkably, there are few data available concerning systemic iron metabolism in Parkinson's disease. We measured total iron binding capacity and circulating iron, ferritin, transferrin, and transferrin receptors; calculated transferrin saturation; and estimated dietary iron intake in patients with idiopathic Parkinson's disease and in controls. Concentrations of circulating iron, ferritin, and transferrin as well as total iron binding capacity and transferrin saturation were significantly lower in patients than controls. There were no differences in transferrin receptors or dietary intake of iron. The decrease in levels of systemic ferritin and transferrin and the total iron binding capacity parallels observations in a Parkinson's disease brain, but the reductions in serum iron concentrations and transferrin saturation do not, and were unexpected. These results suggest the existence of a defect in the systems that regulate the synthesis of the major proteins of iron metabolism in the liver as well as the brain in Parkinson's disease that may, over time, expedite entry of iron into the brain and decrease iron in the extracellular compartment.
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PMID:Altered systemic iron metabolism in Parkinson's disease. 930 29

Although the cause of Parkinson's disease is unknown, oxidative stress has been implicated in its pathogenesis. This theory postulates that normal metabolic processes in the nigrostriatal dopaminergic system may lead to loss of neurons, and that iron-dependent membrane lipid peroxidation may play an important role in the neuronal death. Recent research concerning iron-dependent lipid peroxidation is presented. First, catechols (including dopa and dopamine) and iron form strong oxidizing complexes and induce lipid peroxidation (LPO) in phospholipid liposomes. Active oxygen species including superoxide, hydrogen peroxide, hydroxyl radical and singlet oxygen, do not participate in this LPO, which is inhibited by an excess of dopa (dopamine). Cultured neurons and the substantia nigra are vulnerable to LPO. Second, synthetic melanin prepared by the autooxidation of catechols promotes LPO in the presence of iron. The effects of scavenging agents indicate that this LPO is mediated by superoxide, but not by other oxygen free radicals. Neuronal cell cultures are destroyed by this LPO. Third, catechols and superoxide produced by microglia cause the release of iron from ferritin. Microglia stimulated by phorbol myristate acetate produce superoxide and cause the release of iron from ferritin. Catechols also induce mobilization of ferritin iron. The released iron (i.e. loosely-bound iron) is available to iron-dependent LPO. These data suggest that the biochemical and morphological characteristics of the substantia nigra, which are concomitant with its functional role, provoke iron-dependent lipid peroxidation. It is essential to elucidate how iron bound loosely to low molecules comes into contact with catechols, neuromelanin and superoxide. Drugs that chelate iron site-specifically or modulate the microglial function may bring about some favorable changes in the disease process.
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PMID:[Oxidative stress and the brain]. 943 Sep 79

Ferritin contains most of the iron found in the brain, and the release of iron from ferritin has an essential role in iron-dependent lipid peroxidation. We examined the effect of cultured microglia on the ferritin-dependent lipid peroxidation of phospholipid liposomes monitored by the formation of thiobarbituric acid-reactive substances. Microglia stimulated by phorbol myristate acetate caused lipid peroxidation in the presence of ferritin. This lipid peroxidation was mediated by superoxide produced by the microglia and iron released from the ferritin. Lipid peroxidation 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 iron-dependent lipid peroxidation in the presence of ferritin. 967 69

Tissue iron levels in the extrapyramidal system of earlier- and later-onset Parkinson's disease (PD) subjects were evaluated in vivo using a magnetic resonance imaging (MRI) method. The method involves scanning subjects in both high- and low-field MRI instruments, measuring tissue relaxation rate (R2), and calculating the field-dependent R2 increase (FDRI) which is the difference between the R2 measured with the two MRI instruments. In tissue, only ferritin iron is known to increase R2 in a field-dependent manner and the FDRI measure is a specific measure of this tissue iron pool. Two groups of male subjects with PD and two age-matched groups of normal control males were studied. The two groups of six subjects with PD consisted of subjects with earlier- or later-onset (before or after age 60) PD. FDRI was measured in five subcortical structures: the substantia nigra reticulata (SNR), substantia nigra compacta (SNC), globus pallidus, putamen, and caudate nucleus, and in one comparison region; the frontal white matter. Earlier-onset PD subjects had significant (p < 0.05) increases in FDRI in the SNR, SNC, putamen, and globus pallidus, while later-onset PD subjects had significantly decreased FDRI in the SNR when compared to their respective age-matched controls. Controlling for illness duration or structure size did not meaningfully alter the results. Published post-mortem studies on SN iron levels indicate decreased ferritin levels and increased free iron levels in the SN of older PD subjects, consistent with the decreased FDRI observed in our later-onset PD sample, which was closely matched in age to the post-mortem PD samples. The FDRI results suggest that disregulation of iron metabolism occurs in PD and that this disregulation may differ in earlier- versus later-onset PD.
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PMID:MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects. 1021 76

Iron is found in high concentration in some areas of the brain, and increased iron in the substantia nigra is a feature of Parkinson's disease. The purpose of this study was to investigate the physical environment of brain iron in post-mortem tissue to provide information on the possible role of iron in neurodegeneration in Parkinson's disease. Iron has also been implicated as the cause of signal loss in areas of high brain iron on T2-weighted MRI sequences. Knowledge of the physical environment of the brain iron is essential in interpreting the cause of signal change. Post-mortem tissue was obtained from six cases of Parkinson's disease and from six age-matched controls. Iron levels were measured using absorption spectrophotometry. Extended X-ray absorption fine structure was used to evaluate the atomic environment of iron within the substantia nigra and both segments of the globus pallidus. Cryo-electron transmission microscopy was used to probe the iron storage proteins in these areas. Iron levels were increased in the parkinsonian nigra and lateral portion of the globus pallidus. Spectra from the extended X-ray absorption fine structure experiments showed that ferritin was the only storage protein detectable in both control and parkinsonian tissue in all areas studied. Cryo-electron transmission microscopy studies showed that ferritin was more heavily loaded with iron in Parkinson's disease when compared with age-matched controls. In summary we have shown that iron levels are increased in two areas of the brain in Parkinson's disease including the substantia nigra, the site of maximal neurodegeneration. This produces increased loading of ferritin, which is the normal brain iron storage protein. It is possible that increased loading of ferritin may increase the risk of free radical-induced damage. Differences in ferritin loading may explain regional differences in iron's effect on the T2 signal.
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PMID:Iron in the basal ganglia in Parkinson's disease. An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy. 1021 80

In recent studies, we have found a marked increase in substantia nigra (SN) echogenicity in patients with Parkinson's disease (PD) using transcranial ultrasound. Because a substantial body of evidence has accumulated indicating a selective elevation of iron in the SN from patients with PD, we set out to test the hypothesis that trace metals like iron could lead to the observed increase of SN echogenicity in PD. Rat brains were scanned after stereotactic injection of iron in different concentrations into the SN and after injecting ferritin, zinc and 6-OHDA alone, and after the addition of desferrioxamine. The amount of iron in the SN was measured spectroscopically. For iron, and partly for 6-OHDA, in different concentrations, a dose-dependent increase of SN echogenicity could be visualized, corresponding to an increase of iron measured by spectroscopy. No increase of echogenicity was visualized after the injection of ferritin and the addition of desferrioxamine to 6-OHDA, though an increase of iron was measured by spectroscopy. Therefore, we conclude that iron not bound to these proteins may lead to an increase of echogenicity of the SN.
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PMID:Iron accumulation in the substantia nigra in rats visualized by ultrasound. 1046 17

Parkinson's disease is characterized by dopaminergic cell death in the substantia nigra. The underlying mechanism is, however, unknown. Though there are increasing lines of evidence showing iron accumulation in the Parkinsonian substantia nigra, it still remains obscure whether increased iron is the primary cause of dopaminergic cell death, or just a consequence of the pathological process. It is also unclear how iron gains access to the Parkinsonian SN. To gain more understanding in these areas, the present study investigated the time course of dopaminergic cell death and of changes in the level of iron, ferritin and transferrin. The results showed that iron was increased after the significant nigral dopaminergic cell death induced by 6-hydroxydopamine injection into the rat substantia nigra. On the other hand, the expression of transferrin was decreased. However, there was a temporal increase in the number of ferritin positive microglia. The results indicated that iron increase was not the primary cause of dopaminergic cell death in the Parkinsonian rat. It was most likely the result of an accumulation of iron-laden microglia.
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PMID:Time course of dopaminergic cell death and changes in iron, ferritin and transferrin levels in the rat substantia nigra after 6-hydroxydopamine (6-OHDA) lesioning. 1049 Feb 39

In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.
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PMID:Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. 1060 87

Degeneration of dopaminergic neurons that project from substantia nigra to striatum is the primary mechanism that causes Parkinson disease (PD). This death of dopaminergic cells disturbs control over impulses sent from the motor cortex and hence results in the presence of three cardinal motor signs: tremor, rigidity, bradykinesia. The cause of Parkinson disease is unknown. Current treatments relieve symptoms but do not halt the progression of the disease. It is not yet known what causes neurons to degenerate. Influences of aging, environmental toxins, genetic susceptibility have been pointed out by researchers, but the theory of oxidative stress seems to be the most convincing. It is supposed that SN neurons are exposed to oxidative reactions from dopamine metabolism (production) during which hydrogen peroxide and toxic semiquinones are formed. Additionally, in brains of PD patients there are decreased concentrations of defence mechanisms such as glutathion and compensatory ferritin that binds iron, maintaining it in its safe state (Fe2+ iron takes part in Fenton reaction that leads to free radicals production). However, we have to admit that Parkinson disease is probably multifactorial, and the combination of the above stated factors may cause the disease.
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PMID:[Factors which can play important role in pathogenesis of Parkinson disease]. 1061 5


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