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 distribution of methionine-enkephalin (ME)-like and substance P (SP)-like immunoreactivity in the basal ganglia of untreated schizophrenics as compared with normal control cases, and untreated Huntington and Parkinson patients was studied using the unlabeled peroxidase-antiperoxidase (PAP) method. ME but not SP was reduced in the pallidum of one of six schizophrenics. The remaining five cases showed no differences to the controls. In contrast, no or only very faint homogeneously distributed ME and SP was found in any part of the basal ganglia in Huntington's disease. In Parkinson's disease, SP immunoreactivity was within normal range.
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PMID:Methionine-enkephalin and substance P in the basal ganglia of normals, Parkinson patients, Huntington patients, and schizophrenics. A qualitative immunohistochemical study. 241 7

Neurochemical studies of post-mortem human parkinsonian brains have demonstrated specific alterations in neuropeptide concentrations within the substantia nigra and striatal structures. The drug, 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) has been reported to act as a selective toxin to nigrostriatal dopamine neurons, and induces a parkinsonian-like syndrome in primates. In this study, marmosets developed features typical of Parkinson's disease following treatment with MPTP for four days. The effects of MPTP treatment on the concentrations of dopamine and neuropeptides were determined and changes compared with those reported for Parkinson's disease. It was found that within the substantia nigra, substance P concentrations doubled following treatment with MPTP; in contrast, concentrations of vasoactive intestinal peptide and neuropeptide Y were significantly reduced. No changes were observed in the concentrations of six other neuropeptides measured in this region, notably cholecystokinin. Despite marked depletion of dopamine within the caudate nucleus and putamen, concentrations of all neuropeptides within these structures remained unchanged with the exception of an isolated reduction of neuropeptide Y within the putamen. Somatostatin concentrations within the frontal cortex and hippocampus were significantly elevated in the marmosets treated with MPTP. These neuropeptide changes in the CNS contrast with those reported for Parkinson's disease. In view of the autonomic dysfunction associated with Parkinson's disease, peripheral concentrations of neuropeptides were determined. Significant depletion of neuropeptide Y was identified in the ureter, adrenal and cardiovascular tissue. Thus the neurochemical changes induced by MPTP may not be as selective as previously reported.
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PMID:Neuropeptides and dopamine in the marmoset. Effect of treatment with 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP): an animal model for Parkinson's disease? 241 54

Treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1-4 mg/kg for up to 4 days) caused a profound parkinsonian state. Ten days from the start of MPTP treatment, all animals showed marked motor impairment, consisting of bradykinesia and akinesia, limb rigidity, postural abnormalities, loss of vocalisation and blink reflex, and, on occasions, postural tremor. Measurement of caudate-putamen monoamine content at this time showed a profound loss in 3,4-dihydroxyphenylethylamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid concentrations. Measurement of neuropeptide concentrations in the caudate-putamen, internal and external segments of the globus pallidus, nucleus accumbens, substantia nigra, frontal cortex, and hippocampus showed met-enkephalin, leu-enkephalin, and cholecystokinin (CCK-8) concentrations to be unaffected by MPTP treatment. There was a small decrease in the substance P content of frontal cortex, but otherwise the content of this neuropeptide was unaltered. Parkinsonism in the marmoset, induced by MPTP treatment 10 days earlier, does not alter neuropeptide concentrations in the manner observed in Parkinson's disease.
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PMID:Lack of change in basal ganglia neuropeptide content following subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of the common marmoset. 242 37

Parkinson's disease (PD) is a common condition that is thought to result from a marked degeneration of dopaminergic neurones of midbrain origin. Here I present evidence to show that PD may result from a primary loss of active tachykinin, probably substance P (SP) in the substantia nigra (SN), and that this loss leads to a secondary degeneration of the dopaminergic neurones. This raises the possibility of treating and curing patients with PD by giving them SP agonsts.
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PMID:Substance P and Parkinson's disease: a causal relationship? 243 Dec 25

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 basal ganglia and substantia nigra, taken from control human brain and from patients dying with a diagnosis of Parkinson's disease or Huntington's chorea, were analysed with histochemical and biochemical techniques. The pigmented neurons of the substantia nigra pars compacta possess tyrosine hydroxylase immunoreactivity and are disposed in three major layers, alpha, beta and gamma. This pattern became obscured in choreic brains by the severe shrinkage of the nigra, but total numbers of pigmented neurons were within the normal range. In contrast, pigmented neurons were lost from all layers of the substantia nigra in Parkinson's disease, although examination of cases with minimal cell loss suggested that an internal part of the lateral alpha sub-layer was most severely and consistently affected. A dopaminergic projection between this internal part of the alpha sub-layer and the putamen was suggested by the preferential loss of catecholamines from the putamen in Parkinson's disease. The distribution of the peptides, substance P, methionine-enkephalin and dynorphin 1-17 were mapped immunohistochemically within the substantia nigra. The different patterns of immunoreactive axons and terminals were found to be extensive, at least partially overlapping, and largely avoided the region of the pigmented perikarya of the alpha sub-layer and nucleus paranigralis. All peptides were depleted in choreic substantia nigra, reflecting the degeneration of the striatonigral pathway. However, concentrations of enkephalin-like immunoreactivity were increased within the interpeduncular nucleus. In Parkinson's disease there was a loss of enkephalin- and dynorphin-like immunoreactivity from the substantia nigra but a fall in substance P-like immunoreactivity was only detected by radioimmunoassay, not by immunocytochemistry. Peptide immunoreactivity was also reduced within choreic basal ganglia. However, no gross changes were found in peptide staining of the parkinsonian basal ganglia. In summary we have reported a number of changes in peptide-containing pathways in human degenerative disorders that may reflect the degeneration of neuronal pathways either as a primary event or secondary to initial lesion. We have also emphasized the sensitivity of the alpha sub-layer of nigral neurons to damage in Parkinson's disease. We suggest that the lower density of peptidergic fibres in the area of the perikarya may contribute to the susceptibility of these neurons to damage.
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PMID:Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson's disease and Huntington's chorea. 245 87

Common marmosets were treated daily with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 7-9 mg/kg i.p.) for 25 days, and then kept out of drug for three months before biochemical measurements in various brain areas. This treatment induced a dramatic fall (-80%) in dopamine, homovanillic acid and dihydroxyphenylacetic acid levels in the putamen and caudate nucleus, and a significant but less pronounced reduction (less than or equal to 50%) in the levels of these compounds in the nucleus accumbens. In contrast, the concentrations of four neuropeptides: met-enkephalin, leu-enkephalin, substance P, and cholecystokinin, remained unaltered in all brain areas examined in MPTP-treated marmosets. Therefore the neuropeptide alterations previously reported in Parkinson's disease are probably not secondary to the severe lesion of dopaminergic neurones, but constitute another intrinsic feature of the disease.
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PMID:Levels of Met-enkephalin, Leu-enkephalin, substance P and cholecystokinin in the brain of the common marmoset following long term 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine treatment. 246 6

Substance P is found in both the basal ganglia and cerebral cortex in mammalian brain. In the present study postmortem concentrations of substance P-like immunoreactivity (SP-LI) were measured in the globus pallidus, substantia nigra and 22 cortical regions in a group of demented patients with neuropathological features of both Parkinson's disease (PD) and Alzheimer's disease (AD), and from neurologically normal controls. There were no significant changes in the globus pallidus but concentrations were significantly reduced by 44% in the substantia nigra compacta in the PD patients. In cerebral cortex small (20-30%) significant reductions of SP-LI were found in the PD patients in 7 of 22 cortical regions examined. These results are similar to changes found in AD alone and provide further evidence that the dementia of PD is frequently related to the coincidence of PD and AD.
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PMID:Substance P-like immunoreactivity in brains with pathological features of Parkinson's and Alzheimer's diseases. 247 78

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the primary pathology is thought to be a loss of dopaminergic neurons in the substantia nigra (SN). The mainstay of treatment has been the use of the drug L-DOPA, a drug that crosses the blood-brain barrier and is converted to dopamine. Recently, intracerebrally implanted grafts of adrenal tissue to promote functional recovery in nigral-damaged recipient animals and patients have been successfully performed. The recovery in these cases is said to be due to the dopamine present in the grafted adrenal tissue. This explanation has several fallacies, however. It is the contention of this paper that substance P is the active agent in the grafted tissue. This raises the possibility of improving the treatment for PD by the use of grafted tissue that is a purer source of SP or SP agonists.
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PMID:Adrenal grafting for Parkinson's disease: a role for substance P. 247 50

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


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