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 pathogenesis of Parkinson's disease may be influenced by genetic and environmental factors. Cytochrome P450 mono-oxygenases help to protect against toxic environmental compounds and individual variations in cytochrome P450 expression might, therefore, influence susceptibility to environmentally linked diseases. The frequency of mutant CYP2D6 alleles was studied in 229 patients with Parkinson's disease and 720 controls. Individuals with a metabolic defect in the cytochrome P450 CYP2D6-debrisoquine hydroxylase gene with the poor metaboliser phenotype had a 2.54-fold (95% Cl 1.51-4.28) increased risk of Parkinson's disease. Determination of CYP2D6 phenotype and genotype may help to identify those at greatest risk of Parkinson's disease and may also help to identify the environmental or metabolic agents involved in the pathogenesis of this disease.
 ...
PMID:Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease. 791 91

Debrisoquine (DBQ) metabolism was studied in 80 Parkinson's disease (PD) patients, 26 of whom had young onset Parkinson's disease (YOPD), and in 143 controls. There was no significant difference between the proportion of poor metabolisers of DBQ among YOPD patients compared either to other parkinsonians, or to controls. Nor was there a significant correlation between the age of disease onset and DBQ metabolic ratio (MR). The results do not support the suggestion that impairment of DBQ metabolism (and hence cytochrome P450) is a primary defect in YOPD. However, in comparison with controls, MR values were modestly but significantly higher in PD patients, even in those not treated with drugs known to affect DBQ metabolism.
 ...
PMID:Debrisoquine hydroxylation in Parkinson's disease. 141 26

The metabolism of oral glucurolactone to serum D-glucarate by the hepatic cytochrome P450 enzyme system was no different in 20 untreated Parkinson's disease (PD) patients as compared with 20 age- and sex-matched controls. There was no evidence for a deficit in hepatic enzymes in PD.
 ...
PMID:Metabolism of glucurolactone to glucarate in Parkinson's disease. 151 72

This study aimed to find a possible biochemical basis for the frequent epidemiological observation of a negative correlation between smoking and Parkinson's disease. The effects of cigarette smoke exposure and of beta-naphthoflavone (BNF)-pretreatment on corpus striatal dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied using the mouse MPTP model. Brain and hepatic monoamine oxidase (MAO) activity, hepatic cytochrome P450 content, BNF-inducible ethoxyresorufin O-dealkylase (EROD) activity and corpus striatal dopamine levels were measured. Cigarette smoke exposure partially protected against corpus striatial dopamine depletion by MPTP. This protection was associated with monomaine oxidase (MAO) inhibition in brain and liver, as well as with cytochrome P450 induction. BNF pretreatment also partially protected against MPTP-induced depletion of striatal dopamine. This was associated with a strong induction of cytochrome P450 but not inhibition of MAO activity. Our findings suggest that both MAO inhibition and cytochrome P450 induction may play a role in any biochemical protection afforded by cigarette smoke exposure against the development of Parkinson's disease.
 ...
PMID:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity: partial protection against striato-nigral dopamine depletion in C57BL/6J mice by cigarette smoke exposure and by beta-naphthoflavone-pretreatment. 188 37

The possibility that idiopathic Parkinson's disease may be linked to a deficiency of an important detoxifying enzyme such as the cytochrome P450 enzyme bufuralol hydroxylase is examined. A hypothetical model of how this might operate to produce early onset Parkinson's disease is suggested.
 ...
PMID:Parkinson's disease and cytochrome P450: a possible link? 223 18

Phenytoin-parahydroxylation capacity was determined in 24 patients with Parkinson's disease (PD) and 17 controls. Different function of the phenytoin-metabolizing cytochrome P450 subsystem was found in 6 patients, but in none of the controls. These results add to previous studies suggesting a relation between the pathogenesis of PD and the function of cytochrome P450 subsystems.
 ...
PMID:Cytochrome P450 and Parkinson's disease. Poor parahydroxylation of phenytoin. 237 47

It has been suggested that alterations in the activity of cytochrome P450 monooxygenases may play a role in the pathogenesis of Parkinson's disease, particularly in patients who had onset before the age of 40. We studied the P450-mediated metabolism of acetaminophen to 3-hydroxy-acetaminophen in 26 patients with Parkinson's disease and in 18 control subjects. After subjects ingested 1,000 mg acetaminophen, urine was collected under controlled conditions. Acetaminophen and 3-hydroxy-acetaminophen were measured in the urine using newly developed high-pressure liquid chromatography methods. The ratio of 3-hydroxy-acetaminophen to acetaminophen was calculated for each patient and no significant differences were observed in patients compared with control subjects. Abnormal metabolism was not observed in patients who had onset of Parkinson's disease at or before the age of 40. In addition, no difference in metabolic activity was observed between the patients who were treated with levodopa/carbidopa and those who were not treated. These findings suggest that there are no alterations of P450-mediated metabolism of acetaminophen in patients with Parkinson's disease.
 ...
PMID:Acetaminophen metabolism by cytochrome P450 monooxygenases in Parkinson's disease. 277 16

It is postulated that Parkinson's disease is the result of environmental factors acting on genetically susceptible individuals against a background of normal ageing. Many potentially neurotoxic xenobiotics are detoxified by hepatic cytochrome P450. The function of one such system was studied in forty patients with Parkinson's disease and forty normal control subjects. Significantly more parkinsonian than control subjects had partially or totally defective 4-hydroxylation of debrisoquine. Poor metabolisers of debrisoquine tended to have had earlier onset of disease.
 ...
PMID:Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine. 286 93

CYP2D, a genetically variable isoform of cytochrome P450, has been characterized mainly in the liver and the brain of mammals by measurement of debrisoquine hydroxylase activity. Moreover, 'poor debrisoquine metabolizer' phenotype is significantly increased in Parkinson's disease patients. We present here the first demonstration that the activity of the CYP2D isoform can be characterized in rat brain microsomes by the measurement of dextromethorphan O-demethylase capacity. The cerebral formation of dextrorphan, an antagonist of the N-methyl-D-aspartate receptor, was inhibited by the presence of quinidine and N-methyl-4-phenylpyridinium (MPP+), a dopaminergic neurotoxin inducing a chemical parkinsonism in humans.
 ...
PMID:Dextromethorphan O-demethylase activity in rat brain microsomes. 761 5

Molecular genetic studies of the cytochrome P450 system enzyme CYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in large series of patients with Parkinson's disease (PD) when compared with controls. We have investigated CYP2D6 polymorphism in 91 patients with multiple system atrophy (MSA) in order to determine if this finding is specific to PD or if there is similar evidence of genetic susceptibility to neurotoxicity in MSA. The distribution of CYP2D6 alleles was not significantly different between MSA patients and controls, and there were fewer poor metabolisers in the MSA group than in the control group.
 ...
PMID:CYP2D6-debrisoquine hydroxylase gene polymorphism in multiple system atrophy. 765 42


1 2 3 4 5 6 7 8 9 Next >>