Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. 291 Oct 28

In patients with Parkinson disease, improved visualization of brain iron on a mid-field-strength magnet can be obtained with T2-weighted images and elimination of phase-encoding artifacts. A long echo delay time accentuates the loss of signal from brain iron. However, the long pulse sequence creates phase-encoding artifacts from CSF pulsations at the level of the basal ganglia. These artifacts are eliminated and resolving power increased with additional pulsing in the slice-selective and read gradients. Elimination of motion artifacts enhances visualization of brain iron in three ways: (1) extrapyramidal nuclei containing iron have better definition, (2) abnormalities are better identified, and (3) pseudolesions disappear. Our findings suggest there is significant improvement in the resolving power of brain iron on MR scans made with a mid-field-strength scanner when gradient modification is used.
 ...
PMID:Brain iron in patients with Parkinson disease: MR visualization using gradient modification. 312 74

Significant differences in the content of iron (III) and total iron were found in post mortem substantia nigra of Parkinson's disease. There was an increase of 176% in the levels of total iron and 225% of iron (III) in the substantia nigra of the parkinsonian patients compared to age matched controls. In the cortex (Brodmann area 21), hippocampus, putamen, and globus pallidus there was no significant difference in the levels of iron (III) and total iron. Thus the changes in total iron, iron (III) and the iron (II)/iron (III) ratio in the parkinsonian substantia nigra are likely to be involved in the pathophysiology and treatment of this disorder.
 ...
PMID:Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. 321 14

Akinetic crises are one of the problems arising in patients with Parkinson's disease in particular after long term treatment with levo-dihydroxyphenylalanine (L-DOPA). They are characterized by severe disability to move. Increasing dosages of L-DOPA and decarboxylase or monoaminooxidase inhibitors do not improve these symptoms. Intravenously applied iron in the form of a ferri-ferro-complex exhibits a considerable benefit for all patients treated so far. They regained a remarkable mobility. Their disability score dropped from up to 90 percent down to 30 percent. The effect is dosage-dependent, and withdrawal of iron will lead again to akinetic crises.
 ...
PMID:Improvement of disability and akinesia of patients with Parkinson's disease by intravenous iron substitution. 357 6

Disorders of neurotransmitter balance are observed in Parkinson's disease, pharmacotoxic psychosis and depression. The dopamine-serotonin ratio is reduced to about 20% in Parkinson and pharmacotoxic patients in the caudate nucleus and in the substantia nigra. The serotonin content in these brain areas is lowered only to about 50% in comparison to that of the control, whereas the dopamine level is reduced to 85% in Parkinson patients. This dopamine deficiency has been substituted by exogenous supply of L-dopa in combination with decarboxylase and monoaminooxydase inhibitors. First evidence is presented that L-dopa can be replaced, at least partially, by iron in form of a ferriascorbate complex. This iron compound improves the symptoms of Parkinson's disease to almost the same extent as L-dopa.
 ...
PMID:Dopamine action and disorders of neurotransmitter balance. 365 99

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.
 ...
PMID:Iron uptake by mammalian cortical neurons. 646 62

A clinico-pathological report is given of a case of Parkinson's disease following a general paresis. A 66-year-old male, with no previous history of febrile disease or viral encephalitides, developed a dementing illness. The general paresis was diagnosed from serological studies at the age of 45. He underwent a series of penicillin plus fever therapies as treatment for neurosyphilis. He also developed generalized rigidity and slow mobility 12 years after the diagnosis of general paresis. An anti-Parkinson drug was given. Finally he fell in a state of muteness and became bedridden. He had been hospitalized for 21 years and died from bronchopneumonia. The pathological findings were strikingly similar to post-encephalitic parkinsonism in addition to a healed state of general paresis. They consisted of a widespread nerve cells loss, gliosis and the presence of Alzheimer's neurofibrillary tangles in the substantia nigra. In the cerebral cortex, a diffuse loss of nerve cells and the presence of a weak positive iron reaction were observed. The coexistence of general paresis and post-encephalitic parkinsonism is unusual and the authors discussed the etiological relationship between the two different conditions.
 ...
PMID:Parkinson's disease of post-encephalitic type following general paresis--an autopsied case. 688 16

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)
 ...
PMID:Altered brain metabolism of iron as a cause of neurodegenerative diseases? 751 59

In the absence of identification of either an endogenously or an exogenously derived dopaminergic neurotoxin, the most valid hypothesis currently envisaged for etiopathology of Parkinson's disease (PD) is selective oxidative stress (OS) in substantia nigra (SN). Although OS is not proven, a significant body of evidence from studies on animal and Parkinsonian brain neurochemistry supports it. This hypothesis is based on excessive formation of reactive oxygen species (O2 and OH.) and demise of systems involved with scavenging or preventing the formation of such radicals from H2O2, generated as a consequence of dopamine oxidation (autoxidation and deamination). Since MAO (monoamine oxidase A and B are the major H2O2 generating enzymes in the SN much attention has been paid to their selective inhibitors as symptomatic and neuroprotective agents in PD. Attention should also be given to radical scavengers (e.g. iron chelators, lipid peroxidative inhibitors and Vitamin E derivatives) as therapeutic neuroprotective agents in PD. This is considered valid since a significant elevation of iron is known to occur selectively in SN zone compacta and within the remaining melanized dopamine neurons of Parkinsonian brains. Although all the mechanism of iron induced oxygen free radical formation is not fully known there is no doubt that it participates with H2O2 (Fenton chemistry) to generate cytotoxic hydroxyl radical (OH.) and induce tissue OS and neurodegeneration in 6-hydroxydopamine model of PD. The dramatic proliferation of reactive amoeboid macrophages and microglia seen in SN of PD brains together with OS is highly compatible with an inflammatory process, similar to what has been observed in Alzheimer's disease and multiple sclerosis brains. This has led us to examine the ability of reactive macrophages to produce oxygen free radicals in response to nitric oxide (NO) production. The latter radical has been implicated in the excitotoxicity of glutaminergic neurons innervating the striatum and SN. Indeed we have now observed that in reactive macrophages NO acts as a signal transducer of O2 production which can synergize with dopamine oxidation.
 ...
PMID:Selective MAO-A and B inhibitors, radical scavengers and nitric oxide synthase inhibitors in Parkinson's disease. 752 88

Excess iron (Fe) within the substantia nigra zona compacta (SNc) has been implicated in the pathogenesis of Parkinson's disease (PD). We recently reported that intranigral Fe infusion into the rat substantia nigra (SN) induces dose-dependent SN neurodegeneration and associated reductions in striatal dopaminergic (DA) markers. The objective of the present study was to determine whether infused Fe is capable of inducing persistent/progressive neurodegenerative changes relevant to PD. Following unilateral infusions of vehicle, 1.25 or 2.10 nmol Fe into the rat SN, SNc neuronal loss, SN volume, striatal neurochemical markers, and apomorphine-induced rotational behavior were assessed at 2, 4, and 6 months. Semiquantitative analysis of thionine-stained SNc neurons demonstrated an initial modest neuronal loss which remained stable through 6 months postinfusion. Fe-induced SN atrophy was dose-dependent and progressive through 6 months. Striatal DA and homovanillic acid levels were progressively decreased at least through 4 months following 1.25 nmol Fe infusion; both doses of Fe induced significant reductions of both DA markers at 4 months with no recovery evident through 6 months. Apomorphine-induced rotational behavior progressively increased for both Fe infusion groups through the 6 months of testing. These data indicate that a single exposure of the SN to a modest amount of Fe can induce persistent/progressive changes occurring through a number of months postinfusion and further establishes intranigral Fe infusion as an animal model for PD.
 ...
PMID:Progressive changes in striatal dopaminergic markers, nigral volume, and rotational behavior following iron infusion into the rat substantia nigra. 752 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>