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)

1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as 'at risk' of niacin deficiency, even if not frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.
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PMID:Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa. 47 87

Studies have shown that severe daytime restriction of dietary protein improves the efficacy of L-dopa and reduces response fluctuations in some Parkinson's disease (PD) patients. This study investigated the nutritional adequacy of the daytime restricted-protein diet. Eleven free-living PD patients suffering from unpredictable response fluctuations to L-dopa were counseled to limit protein intake to approximately 10 g before 1700. Three sets of 6-d food records obtained during the 8-wk study showed that while on the test diet, mean intakes of most nutrients remained above the recommended nutrient intakes, although significant decreases occurred in protein, calcium, iron, phosphorus, riboflavin, and niacin intakes. The impact of the test diet on nutritional status as evaluated by changes in body weight and serum prealbumin was small. We conclude that healthy and highly motivated patients can maintain adequate intakes of most nutrients while restricting daytime protein intake. However, nutrient intakes might be compromised in patients whose regular diets are marginally adequate.
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PMID:Effect of daytime protein restriction on nutrient intakes of free-living Parkinson's disease patients. 155 46

In a case-control study, we compared the past dietary habits of 342 Parkinson's disease (PD) patients recruited from nine German clinics with those of 342 controls from the same neighborhood or region. Data were gathered with a structured interview and a self-administered food-frequency questionnaire. Nutrient intakes were calculated from the reported food intakes through linkage with the German Federal Food Code and analyzed using multivariate conditional logistic regression to control for total energy intake, educational status, and cigarette smoking. At the macronutrient level, patients reported higher carbohydrate intake than controls after adjustment for total energy intake, smoking, and educational status (OR = 2.74, 95% confidence interval [CI]: 1.30-6.07, for the highest versus lowest quartile, p trend = 0.02). This was reflected in higher monosaccharide and disaccharide intakes at the nutrient level. There was no difference between patients and controls in protein and fat intake after adjustment for energy intake. We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. There was no difference between groups for alpha-tocopherol intake after adjustment for energy intake. We also found that patients reported a significantly lower intake of niacin than controls (OR = 0.15, 95% CI: 0.07-0.33, p trend < 0.00005). Our results suggest that if antioxidants play a protective role in this disease, the amounts provided by diet alone are insufficient. Although the interpretation of the inverse association between niacin intake and PD is complicated by the high niacin content in coffee and alcoholic beverages, which were also inversely associated with PD in this study, the strength of this association and its biologic plausibility warrant further investigation.
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PMID:Diet and Parkinson's disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study. 922 21

The findings of a negative association between past maize (Zea mays) production and current Parkinson's disease mortality by each prefecture in Japan tends to support the hypothesis that the nutritional condition that causes niacin deficiency might protect people from Parkinson's disease. Specifically, the negative association between both the area planted for dried corn in 1960, 1970 or 1977 and the area planted for sweet corn in 1960 and age-adjusted death rates for Parkinson's disease is ecological evidence supporting the hypothesis. Extending the analysis to other cultivated crops, even stronger negative associations of age-adjusted death rates for Parkinson's disease and cultivation of rice and soybeans were found, but associations were not significant for a large variety of vegetables. The findings for soybean and rice are attributed to the correspondence (co-linearity) of cultivation of these other two seed-crops with maize. Hence, further testing of the theory of niacin deprivation and prevention of Parkinson's disease finds some circumstantial support in the cultivation patterns of a grain of poor niacin and tryptophan availability.
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PMID:Retrospective study of preventive effect of maize on mortality from Parkinson's disease in Japan. 1467 69

Nicotinamide, the amide form of niacin (vitamin B(3)), is the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)) and plays a significant role during the enhancement of cell survival as well as cell longevity. Yet, these abilities of nicotinamide appear to be diametrically opposed. Here we describe the development of nicotinamide as a novel agent that is critical for modulating cellular metabolism, plasticity, longevity, and inflammatory microglial function as well as for influencing cellular life span. The capacity of nicotinamide to govern not only intrinsic cellular integrity, but also extrinsic cellular inflammation rests with the modulation of a host of cellular targets that involve mitochondrial membrane potential, poly(ADP-ribose) polymerase, protein kinase B (Akt), Forkhead transcription factors, Bad, caspases, and microglial activation. Further knowledge acquired in regards to the ability of nicotinamide to foster cellular survival and regulate cellular lifespan should significantly promote the development of therapies against a host of disorders, such as aging, Alzheimer's disease, diabetes, cerebral ischemia, Parkinson's disease, and cancer.
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PMID:Cell Life versus cell longevity: the mysteries surrounding the NAD+ precursor nicotinamide. 1661 Oct 73

A patient with Parkinson's disease taking levodopa/carbidopa, selegiline, buproprion, aspirin and niacin had decreased rigidity and bradykinesia when his niacin dose was steadily escalated for treatment of high triglycerides, but ultimately the patient could not tolerate niacin because of severe nightmares and skin rash. If further research can reproduce this patient's initial beneficial experience while avoiding the adverse effects, niacin could be a useful adjunctive agent for Parkinson's disease, either population-wide or in a pharmacogenomically defined set of responders.
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PMID:Niacin improved rigidity and bradykinesia in a Parkinson's disease patient but also caused unacceptable nightmares and skin rash--a case report. 1666 4

Nicotinamide, the principal form of niacin (vitamin B3), has been proposed to be neuroprotective in Parkinson's disease. However, the effects and mechanisms of nicotinamide on motor function in animals and on mitochondrial function in cellular systems have not been well studied. We hypothesized that niacin-derived NAD(P)H as antioxidants and enzyme cofactors could inhibit oxidative damage and improve mitochondrial function and thus protect neurodegeneration and improve motor function. In the present study, the effects of nicotinamide on mitochondrial function and oxidative stress were studied in a 1-methyl-4-phenylpyridinium (MPP(+))-induced cellular model of Parkinson's disease, and the effects of improving motor dysfunction were studied in an alpha-synuclein transgenic Drosophila Parkinson's model. Mitochondrial function was tested by measuring the activity of mitochondrial complex I and alpha-ketoglutarate dehydrogenase, and oxidative damage was tested by measuring reactive oxygen species, DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine and Comet assay), and protein oxidation (protein carbonyls) levels. Nicotinamide at a relatively higher concentration, that is, 100-fold of the level in the cell culture medium (101 mg/L), significantly protected SK-N-MC human neuroblastoma cells from an MPP(+)-induced decrease in cell viability, complex I and alpha-ketoglutarate dehydrogenase activity, and an increase in oxidant generation, DNA damage, and protein oxidation. In the Drosophila model, nicotinamide at 15 and 30 mg/100 g diet significantly improved climbing ability. These results suggest that nutritional supplementation of nicotinamide at high doses decreases oxidative stress and improves mitochondrial and motor function in cellular and/or Drosophila models and may be an effective strategy for preventing and ameliorating Parkinson's disease.
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PMID:High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson's disease. 1838 61

The factors contributing to substantia nigra pars compacta (SNc) dopamine (DA) neuron death and striatal DA depletion in Parkinson's disease (PD) are still poorly understood. However, mitochondrial dysfunction, cellular energy depletion and oxidative stress appear to play important roles in the pathogenesis of PD. In view of this, the current study examined the potential of nicotinamide, a form of the B-complex vitamin niacin, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced SNc cell loss and striatal DA depletion in two mouse MPTP models that respond differently to putative neuroprotective agents. Adult male C57Bl/6 mice received nicotinamide (125, 250 or 500 mg/kg i.p.) prior to either acute (four injections in 1 day at 2-h intervals) or sub-acute (two injections per day at 4-h intervals for 5 days) MPTP administration. Striatal DA levels, changes in numbers of tyrosine hydroxylase (TH)- and cresyl violet-stained cells in the SNc at 2 and 6 weeks following the last MPTP exposure were analyzed. Nicotinamide administration resulted in a dose-dependent sparing of striatal DA levels and SNc neurons in acute MPTP-treated animals. Only the highest dose of nicotinamide had similar effects in sub-acute MPTP-treated animals. At 6 weeks after MPTP exposure, there was some spontaneous recovery of striatal DA levels in both models: neuroprotective effects were still apparent in acute but not sub-acute MPTP-treated animals. These results show neuroprotective effects of nicotinamide in different mouse Parkinson models associated with different forms of cell death and suggest that nicotinamide may have broad neuroprotective potential in PD.
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PMID:Broad neuroprotective profile of nicotinamide in different mouse models of MPTP-induced parkinsonism. 1870 32

A wide variety of nutritional exposures have been proposed as possible risk factors for Parkinson's disease (PD) with plausible biological hypotheses. Many studies have explored these hypotheses, but as yet no comprehensive systematic review of the literature has been available. MEDLINE, EMBASE, and WEB OF SCIENCE databases were searched for existing systematic reviews or meta-analyses of nutrition and PD, and one meta-analysis of coffee drinking and one meta-analysis of antioxidants were identified. The databases were searched for primary research articles, and articles without robust methodology were excluded by specified criteria. Seven cohort studies and thirty-three case-control (CC) studies are included in the present systematic review. The majority of studies did not find significant associations between nutritional factors and PD. Coffee drinking and alcohol intake were the only exposures with a relatively large number of studies, and meta-analyses of each supported inverse associations with PD. Factors that were reported by at least one CC study to have significantly increased consumption among cases compared with controls were: vegetables, lutein, xanthophylls, xanthins, carbohydrates, monosaccharides, junk food, refined sugar, lactose, animal fat, total fat, nuts and seeds, tea, Fe, and total energy. Factors consumed significantly less often among cases were: fish, egg, potatoes, bread, alcohol, coffee, tea, niacin, pantothenic acid, folate and pyridoxine. In three cohort studies, two reported borderline decreased relative risks and one a significant increased risk with vitamin C intake. One cohort reported an inverse association between caffeine intake and PD. Three cohorts reported significant positive association in men between dairy products and PD.
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PMID:A systematic review of nutritional risk factors of Parkinson's disease. 1907 10

The effects of three hydrazine derivatives on the enzymes of the tryptophan oxidative pathway and of nicotinamide nucleotide synthesis have been studied using preparations from rat liver. The compounds used were Benserazide and Carbidopa, two inhibitors of aromatic amino acid decarboxylase used together with dopa in the treatment of Parkinson's disease, and the anti-tubercular agent isoniazid. All three drugs inhibited tryptophan oxygenase and kynureninase, at concentrations that are likely to be encountered in vivo following administration to patients or experimental animals. Isoniazid, but not Benserazide or Carbidopa, also inhibited 3-hydroxy-anthranilate oxidase and nicotinamide phosphoribosyltransferase. However, these two enzymes were of the drug far in excess of those likely to be encountered in vivo. On the basis of the in vitro enzyme inhibition studies, it is not possible to explain why patients treated with isoniazid (without supplementary vitamin B(6)) develop clinical pellagra, while those treated with Benserazide or Carbidopa do not, despite biochemical evidence of niacin deficiency. It is suggested that this difference may be due either to differences in the intake of dietary niacin in these two groups of patients, or more probably to differences in the metabolism of the drugs and in their interactions with enzymes in vivo that are not apparent in vitro.
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PMID:Inhibition in vitro of the enzymes of the oxidative pathway of tryptophan metabolism and of nicotinamide nucleotide synthesis by benserazide, carbidopa and isoniazid. 2022 44


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