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 parabrachial nucleus is believed to play a role in autonomic regulation. We have used the Fontana-Masson ammoniacal silver nitrate method and a tyrosine hydroxylase-immunostaining technique to demonstrate the presence of neuromelanin-containing catecholaminergic neurons in the parabrachial nucleus of normal individuals. In addition, we also show that there is a significant reduction of these catecholaminergic neurons and presence of Lewy bodies in the parabrachial nucleus of patients with idiopathic Parkinson's disease. These findings may be related to the several autonomic disturbances that may occur in idiopathic Parkinson's disease.
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PMID:Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic Parkinson's disease. 168 Mar 3

Several studies suggest that nitric oxide (NO.) contributes to cell death following activation of NMDA receptors in cultured cortical, hippocampal, and striatal neurons. In the present study we investigated whether 7-nitroindazole (7-NI), a specific neuronal nitric oxide synthase inhibitor, can block dopaminergic neurotoxicity seen in mice after systemic administration of MPTP. 7-NI dose-dependently protected against MPTP-induced dopamine depletions using two different dosing regimens of MPTP that produced varying degrees of dopamine depletion. At 50 mg/kg of 7-NI there was almost complete protection in both paradigms. Similar effects were seen with MPTP-induced depletions of both homovanillic acid and 3,4-dihydroxyphenylacetic acid. 7-NI had no significant effect on dopamine transport in vitro and on monoamine oxidase B activity both in vitro and in vivo. One mechanism by which NO. is thought to mediate its toxicity is by interacting with superoxide radical to form peroxynitrite (ONOO-), which then may nitrate tyrosine residues. Consistent with this hypothesis, MPTP neurotoxicity in mice resulted in a significant increase in the concentration of 3-nitrotyrosine, which was attenuated by treatment with 7 NI. Our results suggest that NO. plays a role in MPTP neurotoxicity as well as novel therapeutic strategies for Parkinson's disease.
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PMID:Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice. 753 Feb 97

It has been suggested that nitric oxide (NO) could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease (PD). To ascertain the possible role of NO as risk factor for PD, we studied the plasma levels of nitrate (oxidation product that provides an indirect estimation of NO), in 68 PD patients and 68 matched-controls. The plasma levels of nitrate did not differ significantly between PD patient and control groups (44.5 +/- 2.46 and 44.8 +/- 2.67 mumol/l, respectively). They were not influenced by antiparkinsonian drug and they did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales and Hoehn and Yahr staging in the PD group. These data suggest that plasma levels of nitrate are apparently unrelated to the risk for PD.
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PMID:Plasma levels of nitrates in patients with Parkinson's disease. 769 96

Nitric oxide (NO) is a recently discovered endogenous mediator of vasodilatation, neurotransmission, and macrophage cytotoxicity. NO is thought to have a function in memory and in long-term potentiation. At high concentrations NO is neurotoxic and may play a role in neurodegeneration. NO is formed from L-arginine by the enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co-factor. Alzheimer's disease (AD) and, to a lesser degree, Parkinson's disease (PD) are thought to be associated with increased microglial activity, suggesting that NO production may be increased. Alternatively, in circumstances of reduced levels of intracellular L-arginine or BH4, NO production is diminished and neurotoxic oxygen radicals may be produced. Since BH4 is decreased in AD and PD brains, these diseases may be associated with decreased NO production. We investigated these two alternatives by measuring the NO degradation products nitrite and nitrate in cerebrospinal fluid (CSF) of PD (n = 103), AD (n = 13), and multiple system atrophy (MSA; n = 14) patients and controls (n = 20). We found for all patient groups, compared with controls, significantly decreased levels of nitrate, but not nitrite. This finding seems to indicate a decreased NO production of the central nervous system (CNS) in these neurodegenerative disorders.
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PMID:Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's disease and multiple system atrophy patients. 813 11

It has been suggested that nitric oxide could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease. Recently, it has been reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in Parkinson's disease patients, assessed with a colorimetric method. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's disease patients and 38 matched controls. The CSF and plasma nitrate levels were not correlated either in patient or in the control group, and they did not differ significantly between the two study groups. They were not influenced significantly by antiparkinsonian drugs in patients, although there was a trend for CSF nitrate levels to be higher in patients treated with levodopa or with dopamine agonists. CSF and plasma nitrate levels did not correlate with age at onset, duration, scores of the unified Parkinson's disease rating scales and Hoehn & Yahr staging in the patients group. These date suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for PD.
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PMID:Cerebrospinal fluid nitrate levels in patients with Parkinson's disease. 874 Nov 30

To investigate whether nitric oxide (NO) plays a role in degenerative neurologic disease (DND), we measured nitrite, nitrate and cyclic GMP in cerebrospinal fluid (CSF) samples from patients with Parkinson's disease (PD), spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS). We found no significant change in CSF nitrite, nitrate or cyclic GMP in patients with any DND compared with control values. These results suggest that NO production is preserved in PD, SCA and ALS.
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PMID:Nitrite, nitrate and cGMP in the cerebrospinal fluid in degenerative neurologic diseases. 874 72

The reactivity of catecholamines with nitrogen oxides formed from NO in aerated solutions, nitrite, and peroxynitrite was evaluated. Dopamine and norepinephrine in aerobic buffer (pH 7.4) were almost completely converted to their 6-nitro-derivatives by nitric oxide (NO) at room temperature, while epinephrine was nitrated and above all oxidized. The products obtained from each catecholamine treated with sodium nitrite at pH 4-7 were compared to those produced by NO at pH 7.4. Peroxynitrite, which can nitrate tyrosinyl residues, did not produce nitro-derivatives, only oxidized ones. The physiological relevance, particularly for the vascular and nervous system, is discussed. Catecholamine oxidation reactions could be relevant to physiological conditions and also explain neurotoxicity in Parkinson's disease and aging. Nitration reactions, requiring such high NO concentrations, do not seem possible to occur directly under normal physiological conditions, but could take place in acidic vesicules where nitrite, catecholamines, and their nitrated products could accumulate. Finally, the ability of dopamine to increase 2',5'-cyclic adenosine monophosphate (cAMP) formation in cultured striatal neurons was blocked by its nitration by NO or its nitrogen oxide derivatives.
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PMID:Oxidation and nitration of catecholamines by nitrogen oxides derived from nitric oxide. 1063 29

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase. We previously demonstrated that administration of 7-NI is effective in blocking MPTP toxicity in both mice and baboons. This was suggested to be due to inhibition of the generation of peroxynitrite which can nitrate tyrosines. In the present study we found increased 3-nitrotyrosine immunoreactivity in the substantia nigra of MPTP treated baboons, which was blocked by coadministration of 7-NI. These findings provide further evidence that peroxynitrite may play a role in MPTP induced parkinsonism in baboons.
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PMID:Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase. 1009 24

Peroxynitrite can nitrate tyrosine residues of proteins. We examined nitrotyrosine-containing proteins in cerebrospinal fluid of 66 patients with neurogenic disease by immunoblot analysis. Nitrated tyrosine residue-containing protein was observed in the cerebrospinal fluid and was concluded to be manganese superoxide dismutase (Mn-SOD). The nitrated Mn-SOD level was strikingly elevated in amyotrophic lateral sclerosis patients and was slightly increased in Alzheimer's and Parkinson's disease patients, whereas an elevated Mn-SOD level was observed only in progressive supranuclear palsy group.
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PMID:Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. 1076 67

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinson's Disease via increasing nitric oxide production.
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PMID:Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production. 1116 97


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