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)

Ferrous ion is an essential cofactor in dopamine synthesis and its decrease may reduce the dopamine production in the nigrostriatal system, the basis of pathogenetic mechanism in Parkinson's disease (PD). Therefore, parkinsonians may have an abnormal systemic ferrokinetics. The serum iron, ferritin, total-iron-binding-capacity (TIBC) levels and transferrin saturation were analysed in 15 patients with Parkinson's disease and 30 controls. The serum iron was lower in PD (95.53 +/- 33.5 micrograms/dl) than in controls (102.5 +/- 32.5 micrograms/dl), but the difference was statistically nonsignificant. The ferritin, TIBC and transferrin saturation were also similar in both groups. The systemic ferrokinetics in our PD was normal, but the ferrokinetics between the central and systemic compartments was different in PD. Therefore, reduction of central dopamine in PD is unlikely due to hypoferruginemia.
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PMID:The serum ferrokinetics in Parkinson's disease. 129 37

Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD.
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PMID:New insights into the cause of Parkinson's disease. 146 74

Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. 147 73

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

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl's and Turnbull's methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe3+ and Fe2+, respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl's stain (Fe3+) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl's technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl's stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson's disease, where iron has been implicated in the pathogenesis.
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PMID:Histochemical distribution of non-haem iron in the human brain. 152 78

The cause of the degeneration of dopamine-containing cells in the zona compacta of the substantia nigra in Parkinson's disease remains unknown. The ability of the selective nigral toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (via its metabolite MPP+) to destroy nigral dopamine cells selectively by inhibiting complex I of the mitochondrial energy chain may provide a clue. Indeed, recent studies of post-mortem brain tissue have suggested the presence of an on-going toxic process in the substantia nigra in Parkinson's disease leading to excess lipid peroxidation. This appears also to involve a disruption of mitochondrial function since mitochondrial superoxide dismutase activity is increased and there is impairment of complex I. These changes may in turn relate to a selective increase in the total iron content of substantia nigra coupled to a generalised decrease in brain ferritin content. Piribedil is used in the symptomatic treatment of Parkinson's disease and is particularly effective against tremor. Piribedil (and its metabolites) acts as a dopamine D-2 receptor agonist. However, in our studies in contrast to other dopamine agonists, in vivo piribedil interacts with dopamine receptors in the substantia nigra and nucleus accumbens but not those in the striatum. In patients with Parkinson's disease the beneficial effects of piribedil may be limited by nausea and drowsiness. Indeed, in MPTP-treated primates piribedil reverses motor deficits but marked side-effects occur. However, pre-treatment with the peripheral dopamine receptor antagonist domperidone prevents the unwanted effects and piribedil produces a profound and longer-lasting reversal of all components of the motor syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parkinson's disease: pathological mechanisms and actions of piribedil. 163 7

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

Ferritin levels were measured in postmortem brain tissue from patients dying with Parkinson's disease [treated with L-3,4-dihydroxyphenylalanine (L-DOPA)] and from control patients. Ferritin levels were decreased in the substantia nigra, caudate-putamen, globus pallidus, cerebral cortex, and cerebellum when compared with age-matched control tissues. However, in CSF from L-DOPA-treated patients and in serum from L-DOPA-treated and untreated parkinsonian patients, ferritin levels were normal. Previous studies have suggested an increased total iron content in substantia nigra of parkinsonian brain. The failure of substantia nigra ferritin formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease. The reason for decreased ferritin levels throughout the parkinsonian brain is not clear but does not seem to reflect a general system deficit in ferritin.
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PMID:Decreased ferritin levels in brain in Parkinson's disease. 235 17

Using radioimmunoassay methods the authors assayed the concentration of biochemical neoplasm markers (BMN) in 106 patients with neurological diseases (M-56, F-50) in the serum, and in 20 cases in the cerebrospinal fluid. In certain cases these markers were present, and sometimes their concentration was raised: ferritin in multiple sclerosis from 200 to 1365 ng/ml, in ischaemic stroke up to 327.9 ng/ml, in Parkinson's disease up to 423 ng/ml in the serum. In some cases of other diseases the levels of carcinoembryonic antigen (CEA), acid prostatic phosphatase (PAP) and alpha-fetoprotein (AFP) were raised, similarly as that of human chorionic gonadotropin (HCG). Further studies are being conducted on BMN, including also other markers (CA 125, CA 199), with monoclonal antibodies, beta-endorphins and prostaglandins in neurological diseases, including multiple sclerosis. It is suggested (Nowak) that BMN may have an indirect role in the aetiology and pathogenesis of certain diseases of the nervous system and that they may have connections with prostaglandins.
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PMID:[Biochemical neoplasm markers in selected neurological diseases]. 243 40


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