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)

Substance P (SP), Met-enkephalin (Met-enk) and cholecystokinin-8-S (CCK-8-S) were measured by a combined HPLC/RIA method in the caudate nucleus and anterior putamen from controls and from Parkinson's disease (PD) patients. SP levels were reduced in caudate in PD, but unchanged in putamen. No differences in Met-enk content were found in parkinsonians compared to controls. However, a significant correlation between DA and Met-enk levels in caudate nucleus from PD was observed. The concentration of CCK-8-S was unaltered in caudate nucleus or putamen in PD. The decrease in caudate nucleus SP levels might be related to the decrease in nigral SP levels in PD, while the reduction in Met-enk levels appears to be a feature of a subgroup of parkinsonian patients.
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PMID:Striatal neuropeptide levels in Parkinson's disease patients. 128 32

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

Neurotransmitters other than dopamine, including neuropeptides, could have important pathophysiologic and therapeutic roles in Parkinson's disease. Both Met-enkephalin, the main transmitter of the striatopallidal pathway, and dynorphin, one of the co-transmitters of the striatonigral pathway display complex anatomic and biochemical interactions with the basal ganglionic dopamine system. In this study, the cerebrospinal fluid content of a proenkephalin derivative, Met5 enkephalin-Arg6-Gly7-Leu8 (MERGL), was found in significantly low concentrations in parkinsonian patients following overnight withdrawal of all medications compared with control subjects, and failed to change after at least 16 h of steady-state, optimal doses of levodopa infusion intravenously. MERGL levels increased with advancing age among normal individuals but not among patients with Parkinson's disease. In contrast dynorphin A(1-8) levels were not different between the two study groups, did not change with levodopa therapy, and failed to correlate with age or any indices of disease progression. These observations, consistent with post-mortem studies on Parkinson brains and contrary to findings in animal models of Parkinsonism, suggest that abnormality of the enkephalin system in this disease is due to involvement of these striatal neurons in the primary pathologic process.
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PMID:Opioid peptides in Parkinson's disease: effects of dopamine repletion. 168 35

Parkinson's disease (PD) is a common neurodegenerative disease of old age characterized by triad of akinesia, rigidity and tremor, reduction of dopamine (DA) content in the nigrostriatum, and severe degeneration of neuron in the substantia nigra. The significant changes after the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rhesus monkeys and C57 black mice are (a) serotonin-like reactions and Parkinsonian symptoms in monkeys and "stickclimbing" disturbance in mice; (b) marked DA reduction in substantia nigra (72.5%), putamen (93.3%), caudate nucleus (91.2%) of monkeys and striatum (94%) of mice; (c) reduction of Met-enkephalin (75%) and Leu-enkephalin (66%) in mouse striatum; and (d) severe degeneration of neurons in the substantia nigra of monkeys and mice. The results suggest that MPTP-treated monkey and C57 black mouse provides useful Parkinsonian animal models and produces behavioral, biochemical and histopathological changes similar to those of human PD.
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PMID:[Experimental research on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian animal models in the rhesus monkey and C57 black mouse]. 216 92

This study concerns the expression of Met-enkephalin (MEnk) in the striatum and the external segment of the globus pallidus proper (GPe) in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). For this purpose, we developed a sensitive immunoperoxidase technique to visualize MEnk-positive patches in routinely prepared formalin-fixed paraffin-embedded striatal tissues. In comparison with normal controls, MEnk-positive patches and pallidal MEnk-positive axon terminals were strongly present in patients with PD, showing characteristic distribution patterns. By comparison, in SND patients, there was striking diminution of MEnk staining in the putamen and ventrolateral portion of the GPe, while MEnk patches were persistent in the caudate nucleus.
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PMID:Met-enkephalin immunoreactivity in the basal ganglia in Parkinson's disease and striatonigral degeneration. 219

No significant alterations in the levels of Met-enkephalin-, Leu-enkephalin-, cholecystokinin- and substance P-like immunoreactive materials were found in 10 areas of postmortem brains from patients with progressive supranuclear palsy (PSP) when compared to controls. These results are at difference with the marked decrease in the levels of enkephalin-, cholecystokinin- and substance P-like immunoreactive materials previously reported in the basal ganglia of parkinsonian patients. Since PSP and Parkinson's disease are both characterized by a severe dopamine nigrostriatal deficit, these results suggest that the decreased brain peptide concentrations found in Parkinson's disease do not simply result from a dopaminergic neuronal loss.
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PMID:Brain neuropeptides in progressive supranuclear palsy. 244 May 13

The changes of the contents of enkephalins in cerebrospinal fluid (CSF) and the action of MIF-1 in rabbit experimental models of Parkinson's disease were studied. In the experiment, the rabbits received injection of 6-hydroxydopamine (6-OH DA) into the unilateral substantia nigra. The contents of Met-enkephalin (MEK) and Leuenkephalin (LEK) in the CSF of the fourth ventricles of the normal control rabbits and those with destructive lesions in the substantia nigra were determined with radio-immunoassay. The concentrations of MEK and LEK in CSF of the rabbit models increased markedly to 14.3 and 28.2 folds in the controls respectively. The increased enkephalin content in CSF could be reduced to the normal level by intravenous administration of MIF-I. The results indicated that the action of MIF-I may be one of the important factors in alleviating the symptoms of parkinsonian patients.
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PMID:[An experimental study on the contents of enkephalins in the cerebrospinal fluid in rabbits with unilateral destructive lesions produced in the substantia nigra and their relation to the regulation of MIF-1]. 257 67

Immunocytochemical studies of the distribution and intensity of Substance P and Met-enkephalin staining in the basal ganglia and substantia nigra were carried out in five cases each of brains from patients with Huntington's disease, Parkinson's disease, Alzheimer's disease, and normal controls. The usefulness of the peroxidase-antiperoxidase method for human autopsy material was confirmed. Substance P and Met-enkephalin fibers were distributed in essentially the same pattern as described in experimental animals and in human brains. In Huntington's disease brains decreased Substance P staining was found in the internal globus pallidus and the substantia nigra, in agreement with radioimmunoassay studies by others. Met-enkephalin staining in the external globus pallidus was of normal intensity, although present within a shrunken area. In Parkinson's and Alzheimer's diseases there was intense immunoreactivity for Substance P in the globus pallidus and substantia nigra, and for Met-enkephalin in the globus pallidus, at variance with reported decreases in Parkinson's disease by radioimmunoassay, but in essential agreement with other immunocytochemical studies. Immunocytochemical methods complement radioimmunoassays of human brain and may help in mapping neuropeptidergic pathways and in pinpointing abnormalities in these pathways in basal ganglia disorders.
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PMID:Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases. 257 85

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.
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PMID:Brain neurotransmitters and neuropeptides in Parkinson's disease. 609 88

A motor disorder similar to idiopathic Parkinson's Disease develops in rhesus monkeys after several daily repeated doses of N-methyl-4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). The concentrations of peptides derived from proenkephalin A, proenkephalin B, substance P and somatostatin were measured by specific radioimmunoassays in the basal ganglia of MPTP-treated monkeys. In MPTP-treated monkeys, dynorphin B concentration was reduced in the caudate. In the putamen, the concentrations of peptides derived from both proenkephalin A and proenkephalin B were decreased. In the globus pallidus, the concentrations of all opioid peptides tend to be increased, reaching significance only for alpha-neo-endorphin. In the substantia nigra, only Met-enkephalin concentration was reduced, while other peptides derived from either proenkephalin A or proenkephalin B were not changed. Substance P and somatostatin were not changed in any brain area examined. Some of the symptoms associated with Parkinson's Disease may be related to altered activity of endogenous opiates in basal ganglia.
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PMID:Primate model of Parkinson's disease: alterations in multiple opioid systems in the basal ganglia. 615 Jul 50


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