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 degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson's disease (PD). However, the etiology of this degeneration is not known. Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease. An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper. The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN). Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD.
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PMID:Oxidative stress: a role in the pathogenesis of Parkinson's disease. 219 8

A 12-year-old boy developed occasional attacks of oculogyric crisis after physical exercises or when tired. Following the initial symptom, progressive Parkinsonian features such as bradykinesia, muscular rigidity, hand tremors in posture, mild dysarthria and disorder of postural reflexes developed. There was no marked diurnal fluctuation o symptoms. Serum ceruloplasmin, copper levels, cranial X-ray CT scan and MRI were normal. Measurement of the plasma levels of L-dopa after single oral administration (300 mg) were normal. The treatment with L-dopa improved the Parkinsonian features excluding the attacks of oculogyric crisis in a few weeks. This case is not identical with juvenile Parkinsonism proposed by Yokochi et al for lack of both crural or truncal dystonia and remarkable response to L-dopa. Oculogyric crisis is known in several patients with severe generalized dystonia, and seldom in patients with Parkinson disease or juvenile Parkinsonism. Oculogyric crisis may be one of focal dystonias confined to extraocular muscles.
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PMID:[Oculogyric crisis as an initial symptom of juvenile parkinsonism-like disease]. 260 35

Levels of iron, copper, zinc, manganese, and lead were measured by inductively coupled plasma spectroscopy in parkinsonian and age-matched control brain tissue. There was 31-35% increase in the total iron content of the parkinsonian substantia nigra when compared to control tissue. In contrast, in the globus pallidus total iron levels were decreased by 29% in Parkinson's disease. There was no change in the total iron levels in any other region of the parkinsonian brain. Total copper levels were reduced by 34-45% in the substantia nigra in Parkinson's disease; no difference was found in the other brain areas examined. Zinc levels were increased in substantia nigra in Parkinson's disease by 50-54%, and the zinc content of the caudate nucleus and lateral putamen was also raised by 18-35%. Levels of manganese and lead were unchanged in all areas of the parkinsonian brain studied when compared to control brains, except for a small decrease (20%) in manganese content of the medial putamen. Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death.
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PMID:Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. 272 38

Following the intravenous infusion of oxyferriscorbone into the tail vein of the rat, the blood and brain metal ion content was measured over the following 72 h period. Administration of oxyferriscorbone increased the total iron content of blood for up to 24 h following intravenous infusion. In contrast, there was no increase in the total iron content of the cerebellum or striatum. Overall, there was no change in total zinc or copper content of the blood or brain following oxyferriscorbone administration. The effect of oxyferriscorbone in Parkinson's disease may not be related to any alteration in total iron content of the brain.
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PMID:Oxyferriscorbone elevates the total iron content of blood but not brain. 273 8

The total activity of superoxide dismutase (SOD) and cytosolic and particulate activity of SOD in human substantia nigra and cerebellum were measured by a spectrophotometric method based on the ability of SOD to inhibit the autoxidation of adrenaline. The cytosolic and particulate isoenzymes of SOD were differentiated by the inclusion of potassium cyanide which selectively inhibits cytosolic copper/zinc-dependent SOD activity. In autopsied human brains, there was no difference in total SOD activity, or the activity of SOD in cytosol in substantia nigra of patients dying with Parkinson's disease compared to age-matched controls. However, the activity of the particulate form of SOD was higher in the parkinsonian substantia nigra compared to control tissue. In the cerebellum there was no difference in the total, cytosolic, or particulate activity of SOD between parkinsonian patients and age-matched controls. Increased activity of SOD in particulate fraction may be a protective response to elevated levels of toxic free radicals in the parkinsonian substantia nigra. Alternatively, increased SOD activity may induce cell death through the accumulation of hydrogen peroxide.
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PMID:A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra. 276 Jun 16

Metal deficiency or toxicity states have been recognized as a cause of several neurological disorders and are suspected in others. We analyzed four brain regions (frontal cortex, caudate nucleus, substantia nigra, and cerebellum) in 36 human brains for concentrations of 24 metals (Ag, Al, As, B, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Pb, Mg, Mn, Mo, Na, Ni, P, Se, Ti, V, W, Zn). Regional metal concentrations, measured using atomic absorption and atomic emission spectroscopy, were compared between 9 Parkinson's disease (PD) brains, 15 brains from patients with other chronic neurological diseases, and 12 control brains. No significant metal concentration differences were noted between brains from PD and other chronic neurologic disease. However, parkinsonian brains (PD and parkinsonism secondary to neurofibrillary tangle disease) showed lower concentrations of magnesium in the caudate nucleus and copper in the substantia nigra than control brains. These findings may represent an etiologically important clue to parkinsonism.
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PMID:Regional metal concentrations in Parkinson's disease, other chronic neurological diseases, and control brains. 276 23

The cerebrospinal-fluid copper concentration, measured by electrothermal atomisation/atomic absorption spectrophotometry, was significantly higher in 24 patients with untreated, idiopathic Parkinson's disease than in a control population of 34 patients (p less than 0.001). The difference in the in-vitro capacity of copper to damage DNA, measured by the phenanthroline assay was even greater. The high phenanthroline-copper concentration correlated with disease severity (p = 0.02) and with the rate of progression of disease (p less than 0.05). A possible role is suggested for copper-catalysed oxidative mechanisms in the pathogenesis of Parkinson's disease.
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PMID:Raised cerebrospinal-fluid copper concentration in Parkinson's disease. 288 15

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

The stability constants of the mixed ligand complexes of L-dopa, L-tyrosine, L-phenylalanine, and dopamine with copper(II) and nickel(II) ions and with 2,2'-bipyridyl and 1,10-phenanthroline were determined pH-metrically at 25 degrees C and an ionic strength of 0.2 mol/dm3 (KCl). Spectral studies were made to establish the binding mode of the ambidentate L-dopa in the ternary complexes. In contrast with the aromatic (N,N) donor atoms, the (O,O) binding mode of L-dopa is particularly favored in its ternary systems with copper(II) and nickel(II); thus, even at physiological pH there is a very considerable formation of (O,O)-bound mixed ligand complexes containing a free amino acid side-chain. Numerous binary transition metal-L-dopa complexes and the ternary complexes formed with various B ligands have been evaluated from a coordination chemistry aspect, with regard to the possibility of their therapeutic application in the treatment of Parkinson disease.
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PMID:Copper(II) and nickel(II) ternary complexes of L-dopa and related compounds. 407 70

Free radicals are highly reactive chemical species with an unpaired electron, and their formation is catalyzed by transition metals like iron, copper, and manganese. There have been numerous studies linking free radical damage with neuropsychiatric illnesses, including several psychiatric and motor disorders, raising the possibility that antioxidant strategies might serve a neuroprotective role for some conditions. The illnesses studied include tardive dyskinesia, schizophrenia, Parkinson's disease, and Alzheimer's disease. Although oxidative mechanisms may play a role in these conditions, further studies are necessary to define their involvement, and to determine the extent to which antioxidants may partially alleviate or prevent some of these conditions.
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PMID:Free radical involvement in neuropsychiatric illnesses. 767 80


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