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)

2-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline were identified for the first time as novel endogenous amines in parkinsonian and normal human brains by gas chromatography-mass spectrometry. It is of interest that these tetrahydroisoquinolines are analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which produces Parkinson's disease.
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PMID:Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, novel endogenous amines, in parkinsonian and normal human brains. 204 84

Treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or (+)-methamphetamine (METH) results in regionally heterogeneous patterns of dopaminergic depletion. The magnitude of the MPTP-induced dopamine (DA) depletion corresponds directly to the density of [3H]mazindol binding to DA transport sites, but not the DA concentration, in intact mouse striatal regions. In contrast, the extent of METH-induced DA depletion corresponds to the intact dopamine concentration, not the [3H]mazindol binding, in the same striatal regions. The findings provide a rationale for testing different hypotheses regarding the neurobiological substrates of mesostriatal injury in idiopathic Parkinson's disease (PD).
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PMID:Contrasting tissue factors predict heterogeneous striatal dopamine neurotoxicity after MPTP or methamphetamine treatment. 207 99

The present study was performed to determine the effect of a nearly complete nigrostriatal dopaminergic denervation on DARPP-32 levels in the striatum from animals and parkinsonian patients. DARPP-32 levels were estimated by in vitro phosphorylation in the presence of cAMP, or after inactivation of endogenous kinases and phosphatases, in the presence of the catalytic subunit of cAMP-dependent protein kinase. Intranigral 6-hydroxydopamine (6-OHDA) infusion in rats, or peripheral administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets, did not change striatal DARPP-32 levels. Postmortem studies, carried out on brains obtained shortly after death, from patients with Parkinson disease, or from patients with progressive supranuclear palsy, showed that the levels of striatal DARPP-32 were not different from controls. These results indicate that dopaminergic striatal denervation did not modify the amount of DARPP-32 in the striatum, suggesting that the expression of DARPP-32, a protein which mediates some of the effects of dopamine in striatal neurons, is independent from the dopaminergic innervation.
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PMID:Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man. 210 23

The discovery of profound dopamine depletion of basal ganglia in patients with Parkinson's disease and the development of antiparkinsonian drug therapy were largely based on animal models. The behavioural changes caused by cholinergic drugs, reserpine and related agents, and unselective neuronal lesions were the first widely used animal models for Parkinson's disease. The crucial breakthrough was the observation of the circling behaviour in rodents after unilateral intranigral injection of 6-hydroxydopamine. This Ungerstedt model still is one of the basic animal models of Parkinson's disease. It is suitable for the screening of new potential antiparkinsonian agents with the classic spectrum. The parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and the monkey is the latest and the best animal model for Parkinson's disease. Especially when given to the monkey, MPTP causes biochemical, behavioural and neuropathological changes which largely mimick those of Parkinson's disease in man. The MPTP-induced parkinsonism in the monkey can be used for the study of the neurobiology and new forms of drugs therapy of Parkinson's disease. However, because the MPTP monkey model is expensive and laborious, it is not particularly convenient for the screening of new drugs. Recently, a new approach in the treatment of Parkinson's disease is to develop drugs which might prevent or retard the disease progression. The prevention of behavioural changes of aged rodents is used as an animal model and promising results with selegiline have been obtained.
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PMID:Animal models of parkinsonism. 212 84

The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochrome c reductase activities were significantly reduced, whereas succinate cytochrome c reductase activity was normal. These results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that Parkinson's disease may be due to an environmental toxin with action(s) similar to those of MPTP.
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PMID:Mitochondrial complex I deficiency in Parkinson's disease. 215 50

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

In human and subhuman primates, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, biochemical and neuropathological alterations highly reminiscent of those observed in Parkinson's disease. The MPTP model has provided the best available tool to date for the assessment of efficacy and side-effects of symptomatic treatments of Parkinson's disease. In addition, the mechanism of action of MPTP has offered a basis for the development of novel therapeutic strategies aimed at the prevention of Parkinson's disease.
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PMID:The MPTP model: versatile contributions to the treatment of idiopathic Parkinson's disease. 220 10

To assess the stability of neural deficits produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the performance of monkeys on an object retrieval (detour) task was studied. The task required retrieval of a banana slice from a transparent box open on one side and fastened to a tray in front of the cage. The orientation of the open side, position on the tray, and position of the banana in the box were manipulated to vary the difficulty of the trials. Six African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative doses over 4-5 days) and compared with 5 saline-treated control monkeys. The MPTP-treated monkeys had no gross neurological deficits but did have motor and cognitive deficits during acquisition of the object retrieval task 8-12 months after treatment (J. R. Taylor, Elsworth, Roth, Sladek, & Redmond, in press). Performance on the task was examined for 3 months after it had been learned. The MPTP-treated subjects reached at the barrier (transparent side) significantly more than controls and were less successful at retrieving the reward on the 1st reach than controls. Although they took longer to initiate the reach and had more motor problems than controls, they were as likely as controls to retrieve the reward in the end. These deficits remained stable throughout testing. An opaque but otherwise identical box was used randomly on some trials. MPTP-treated subjects decreased barrier reaches to control levels on trials in which the opaque box was used, whereas motor problems increased compared with trials in which the transparent box was used. The task can detect subtle performance deficits similar to those found in Parkinson's disease.
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PMID:Cognitive and motor deficits in the performance of an object retrieval task with a barrier-detour in monkeys (Cercopithecus aethiops sabaeus) treated with MPTP: long-term performance and effect of transparency of the barrier. 220 26

We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity.
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PMID:GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice. 225 Jan 72

The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease.
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PMID:Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease. 227 21


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