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)

Cysteine (CYS) is a non-essential amino acid which elicits excitotoxic properties via the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. CYS levels are known to be elevated in association with neurological disease such as Alzheimers Disease (AD) and Parkinsons Disease (PD). We have previously reported studies investigating the toxicity of CYS and its major metabolite cysteinesulfinic acid (CSA) to human neuronal cell lines in vitro and in continuation of this we now report the toxicity of other compounds (Homocysteic Acid, HCA; Homocysteine, HCYS; and Cysteic Acid, CA) in the CYS metabolic pathway. Three cell lines, all of human origin and derived from separate discrete areas of the brain were used in the neurotoxicity assays. Lactate dehydrogenase (LDH) release was assayed as a measure of cell death. The cell lines investigated showed varying degrees of toxic responses which were the reverse of those seen when they were exposed to CYS or CSA. The SK.N.SH (Neuroblastoma) cell line, which exhibits a high toxic response to CYS and CSA, gave a low toxic response to HCA and CA while the TE 671 (Medulloblastoma) cell line, which exhibits a low toxic response to CYS and CSA, showed a high toxic response to HCYS, HCA and CA. However, the U-87 MG (Glioblastoma) cell line, which has a median toxic response to CYS and CSA, also has median response to HCYS, HCA and CA. These results show that toxic responses are cell-type specific for CYS and its metabolites and this may be reflected in the patterns of neurodegeneration observed in such diseases as AD and PD. HCYS is selectively toxic to medulloblastoma cells; this may explain why high HCYS levels result in neural tube defects in prenatal humans, where the same cell-type is involved.
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PMID:In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines. 974 17

Although the cause of Parkinson's disease (PD) is unknown, data suggest roles for environmental factors that may sensitize dopaminergic neurons to age-related dysfunction and death. Based upon epidemiological data suggesting roles for dietary factors in PD and other age-related neurodegenerative disorders, we tested the hypothesis that dietary folate can modify vulnerability of dopaminergic neurons to dysfunction and death in a mouse model of PD. We report that dietary folate deficiency sensitizes mice to MPTP-induced PD-like pathology and motor dysfunction. Mice on a folate-deficient diet exhibit elevated levels of plasma homocysteine. When infused directly into either the substantia nigra or striatum, homocysteine exacerbates MPTP-induced dopamine depletion, neuronal degeneration and motor dysfunction. Homocysteine exacerbates oxidative stress, mitochondrial dysfunction and apoptosis in human dopaminergic cells exposed to the pesticide rotenone or the pro-oxidant Fe(2+). The adverse effects of homocysteine on dopaminergic cells is ameliorated by administration of the antioxidant uric acid and by an inhibitor of poly (ADP-ribose) polymerase. The ability of folate deficiency and elevated homocysteine levels to sensitize dopaminergic neurons to environmental toxins suggests a mechanism whereby dietary folate may influence risk for PD.
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PMID:Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. 1179 48

Moderate hyperhomocysteinaemia has been linked to an increased risk for cardiovascular diseases. Increased homocysteine concentrations may follow folate depletion due to insufficient dietary intake of the vitamin, but there is also some indication that immune activation could play a role. In this preliminary study, homocysteine, folate, and vitamin B(12) concentrations were measured in 19 patients with Parkinson's disease, 61-90 years of age, and compared to a healthy control group of similar age and to neopterin concentrations as an indicator of immune activation. A subgroup of patients presented with increased homocysteine and low folate concentrations. Homocysteine levels correlated inversely with vitamins folate and B(12) and positively with neopterin concentrations. Disturbed homocysteine metabolism in Parkinson's disease may be associated with vitamin deficiency and with immune system activation which may underlie folate depletion.
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PMID:Moderate hyperhomocysteinaemia and immune activation in Parkinson's disease. 1248 85

In recent years, an intense interest has developed in the association between Parkinson's disease (PD) and hyperhomocysteinemia. Homocysteine (Hcy) is a neuronal excitotoxic amino acid, and is well known as a risk factor for vascular diseases. Some reports suggest that the administration of L-DOPA may promote hyperhomocysteinemia and idiopathic atherosclerosis. In this study, we report that a mild hypertrophy of the intima-media complex (IMC) of the carotid artery, which has been established as a marker for systemic atherosclerosis, is observed in PD patients compared with normal subjects. PD patients that were treated with L-DOPA for long durations showed a hypertrophic IMC, while the patients that were not treated with L-DOPA did not show any hypertrophic changes in the IMC. These hypertrophic changes were observed primarily in patients with a Hoehn-Yahr stage of 3-5. PD patients with hypertrophic IMC of the carotid artery also exhibited elevated plasma levels of Hcy associated with the C677T genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). Moreover, a prolonged duration of treatment with L-DOPA in patients with MTHFR T/T genotype enhanced the hypertrophy of IMC, compared with patients with the C/C or C/T genotype. These results suggest that hyperhomocysteinemia promoted by the C677T genotype of MTHFR and prolonged treatment with L-DOPA enhances atherosclerosis in PD patients and affects their general condition.
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PMID:Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype. 1261 26

The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders. The databases MEDLINE, Current Contents and EMBASE were searched (between 1966 and 2002) for English language publications with the key words 'Homocysteine' and 'Stroke'; 'Alzheimer Disease'; 'Cognitive Impairment'; 'Epilepsy'; 'Depression'; or 'Parkinson's disease'. Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect. Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals. The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid. More research evidence is necessary before population screening can be recommended.
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PMID:[Homocysteine and neuropsychiatric disorders]. 1505 41

Elevated plasma homocysteine is a risk factor for cardiovascular disease and Alzheimer's disease. To understand the factors that determine the plasma homocysteine level it is necessary to appreciate the processes that produce homocysteine and those that remove it. Homocysteine is produced as a result of methylation reactions. Of the many methyltransferases, two are, normally, of the greatest quantitative importance. These are guanidinoacetate methyltransferase (that produces creatine) and phosphatidylethanolamine N-methyltransferase (that produces phosphatidylcholine). In addition, methylation of DOPA in patients with Parkinson's disease leads to increased homocysteine production. Homocysteine is removed either by its irreversible conversion to cysteine (transsulfuration) or by remethylation to methionine. There are two separate remethylation reactions, catalyzed by betaine:homocysteine methyltransferase and methionine synthase, respectively. The reactions that remove homocysteine are very sensitive to B vitamin status as both the transsulfuration enzymes contain pyridoxal phosphate, while methionine synthase contains cobalamin and receives its methyl group from the folic acid one-carbon pool. There are also important genetic influences on homocysteine metabolism.
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PMID:Methylation demand: a key determinant of homocysteine metabolism. 1521 38

Homocysteine is a thyol amino acid resulting from a methylation of methionine, an essential amino acid derived from dietary proteins. Homocysteine is metabolized through two pathways: remethylation and transsulfuration, which use as confactors folic acid, vitamin B6 and vitamin B12. The genetic and acquired factors that induce a reduction of levels of folic acid, vitamin B6 and vitamin B12 cause an increase of plasma levels of homocysteine. Numerous clinical studies showed a relationship between hyperhomocysteinemia, cerebrovascular diseases and Alzheimer disease. The hyperhomocysteinemia is also demonstrated in patients with Parkinson disease treated with levodopa and in the epileptic patients treated with anticonvulsant drugs. Nevertheless, so far it is not fully clear how significant is the relationship between the hyperhomocysteinemia and the above-mentioned neurological diseases.
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PMID:[Hyperhomocysteinemia in neurologic diseases]. 1530 48

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT-I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT-I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT-I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa-treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT-I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT-I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT-I effectively reduces HHcy.
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PMID:Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients. 1539 46

Homocysteine (HC) and dehydroepiandrosterone sulphate (DHEAS) plasma levels have been evaluated in groups of male and female patients with Parkinson's disease (PD) and in a group of female patients with Alzheimer's disease (AD) and compared with the corresponding plasma levels observed in a group of age-matched subjects. It has been confirmed that HC plasma levels are enhanced in both PD and AD patients. As far as the DHEAS plasma levels are concerned no changes have been observed in PD patients while a marked decrease has been observed in AD patients. These results support the view that while the pro-oxidant effects of HC and its agonist action at NMDA receptors can play a role in both neurodegenerative diseases, the role of DHEAS is more complex and may be an important factor only in certain neurodegenerative diseases. Thus, according to the present study DHEAS is likely to be involved in AD but not in PD.
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PMID:Studies on homocysteine and dehydroepiandrosterone sulphate plasma levels in Alzheimer's disease patients and in Parkinson's disease patients. 1554 16

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. L-dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinson's disease (PD) patients. Folate and cobalamin status also seems to influence the effects of L-dopa on plasma Hcy levels; therefore B-vitamins supplementation has been proposed to reduce the HHcy in L-dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with L-dopa in the baseline condition and following a 5-week period of treatment with cobalamin and folate; results were compared with 35 controls. Analysis of data revealed that Hcy levels were higher in L-dopa treated PD patients when compared with age- and sex-matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.
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PMID:Hyperhomocysteinemia in L-dopa treated Parkinson's disease patients: effect of cobalamin and folate administration. 1580 66


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