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)

During the past 20 years graphonomic research has become a major contributor to the understanding of human movement science. Graphonomic research investigates the relationship between the planning and generation of fine motor tasks, in particular, handwriting and drawing. Scientists in this field are at the forefront of using new paradigms to investigate human movement. The 16 articles in this special issue of Human Movement Science show that the field of graphonomics makes an important contribution to the understanding of fine motor control, motor development, and movement disorders. Topics discussed include writer's cramp, multiple sclerosis, Parkinson's disease, schizophrenia, drug-induced parkinsonism, dopamine depletion, dysgraphia, motor development, developmental coordination disorder, caffeine, alertness, arousal, sleep deprivation, visual feedback transformation and suppression, eye-hand coordination, pen grip, pen pressure, movement fluency, bimanual interference, dominant versus non-dominant hand, tracing, freehand drawing, spiral drawing, reading, typewriting, and automatic segmentation.
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PMID:Advances in graphonomics: studies on fine motor control, its development and disorders. 1702 11

Caffeine is a nonselective competitive blockade of adenosine A1 and A2A receptors. In this report, we studied the efficacy of 100 mg of caffeine per day on the freezing of gait (FOG) for patients with Parkinson's disease. Different subtypes of FOG showed different therapeutic responses to caffeine. Caffeine improved "total akinesia" type of FOG, but had no effect on "trembling in place." Tolerance developed to the beneficial effect of caffeine on FOG within a few months, but a 2-week caffeine withdrawal period could restore the effect of caffeine.
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PMID:Effects of caffeine on the freezing of gait in Parkinson's disease. 1737 24

Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.
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PMID:Caffeine analogs: biomedical impact. 1751 58

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin causing symptoms that resemble those observed in patients suffering from Parkinson's disease. However, in animal or human organisms, MPTP is converted to MPDP(+) (1-methyl-4-phenyl-2,3-dihydropyridinium) and further to MPP(+) (1-methyl-4-phenylpyridinium); the latter compound is the actual neurotoxin. In this report, we demonstrate that MPDP(+) and MPP(+) can form stacking complexes with methylxanthines (caffeine and penthoxifylline), which leads to significant impairment of the biological activity of these toxins (as measured by their mutagenicity).
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PMID:Impaired mutagenic activities of MPDP(+) (1-methyl-4-phenyl-2,3-dihydropyridinium) and MPP(+) (1-methyl-4-phenylpyridinium) due to their interactions with methylxanthines. 1753 33

Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caffeine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; p(trend) = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; p(trend) = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease.
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PMID:Plasma urate and risk of Parkinson's disease. 1828 33

The selection and execution of appropriate motor behavior result in large part from the ability of the basal ganglia to collect, integrate and feedback information coming from the cerebral cortex. The GABAergic medium spiny neurons (MSNs) of the striatum represent the main receiving station of the basal ganglia. These cells are innervated by excitatory glutamatergic fibers from cortex and thalamus, and modulatory dopaminergic fibers from the midbrain. MSNs comprise two populations of projection neurons, which give rise to the direct, striatonigral pathway, and indirect, striatopallidal pathway. Changes in transmission at the level MSNs affect the activity of thalamocortical projection neurons, thereby influencing motor behavior. For instance, the cardinal symptoms of Parkinson's disease, such as tremor, rigidity and bradykinesia, are caused by the selective degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, which modulate the activity of MSNs in the dorsal striatum. The therapy for Parkinson's disease relies on the use of levodopa, but is hampered by neuroadaptive changes affecting dopaminergic and glutamatergic transmission in striatonigral neurons. MSNs are also the target of many psychoactive drugs. For example, caffeine affects motor activity by blocking adenosine receptors in the basal ganglia, thereby affecting neurotransmission in striatopallidal neurons. The present review focuses on studies performed in our laboratory, which provide a molecular framework to understand the effects on motor activity of adenosine and caffeine.
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PMID:Signaling in the basal ganglia: postsynaptic and presynaptic mechanisms. 1758 65

Erectile dysfunction is common among individuals with Parkinson's disease, but it is unknown whether it precedes the onset of the classic features of Parkinson's disease. To address this question, the authors examined whether erectile dysfunction was associated with Parkinson's disease risk in the Health Professionals Follow-up Study. Analyses included 32,616 men free of Parkinson's disease at baseline in 1986 who in 2000 completed a retrospective questionnaire with questions on erectile dysfunction in different time periods. Relative risks were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, history of diabetes, and other covariates. Among men who reported their erectile function before 1986, 200 were diagnosed with Parkinson's disease during 1986-2002. Men with erectile dysfunction before 1986 were 3.8 times more likely to develop Parkinson's disease during the follow-up than were those with very good erectile function (relative risk = 3.8, 95% confidence interval: 2.4, 6.0; p < 0.0001). Multivariate-adjusted relative risks of Parkinson's disease were 2.7, 3.7, and 4.0 (95% confidence interval: 1.4, 11.1; p = 0.008) for participants with first onset of erectile dysfunction (before 1986) at 60 or more, 50-59, and less than 50 years of age, respectively, relative to those without erectile dysfunction. In conclusion, in this retrospective analysis in a large cohort of men, the authors observed that erectile dysfunction was associated with a higher risk of developing Parkinson's disease.
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PMID:Erectile function and risk of Parkinson's disease. 1787 83

Our objective was to assess the association between risk factors for Parkinson's disease (PD) and abnormal olfaction in first-degree relatives of patients with PD. Factors including lower cigarette smoking and lower caffeine consumption have been associated with increased risk of PD. Idiopathic hyposmia has also been associated with an increased risk of PD. The relationship between risk factors for PD and impaired olfactory function has not been evaluated in relatives of PD patients. We conducted a mail survey of odor identification ability in 173 first-degree relatives of PD patients using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Respondents also completed a questionnaire inquiring about risk factors for PD including caffeine consumption, tobacco use, exercise, and exposures to heavy metals, well-water, and pesticides. There was a direct relationship between olfactory performance and lifetime caffeine intake. After adjustment for age, gender, and smoking status, subjects who reported drinking 2 to 3 cups of caffeinated beverages per day (2.6 points higher 95% CI: 0.5, 4.5) and 4 or more cups per day (3.7 points higher, 95% CI: 0.6, 6.7) had significantly better UPSIT scores than those who consumed less than 1 cup per day. There was no significant relationship between olfactory performance and other risk factors. In conclusion, abnormal olfaction is associated with significantly lower lifetime caffeine consumption in first-degree relatives of PD patients. Further research is warranted to determine whether a history of lower caffeine consumption confers additional risk for the development of PD in hyposmic relatives of PD patients.
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PMID:Risk factors for Parkinson's disease and impaired olfaction in relatives of patients with Parkinson's disease. 1787 51

Besides dopaminergic deficiency, other neurotransmitter systems such as noradrenergic nuclei are affected in Parkinson's disease. Locus coeruleus degeneration might influence the response to dopamine replacement and the presence of long-term complications such as dyskinesias. In this scenario of noradrenergic and dopaminergic neurodegeneration, behavioural effects induced by dopaminergic-interacting drugs are incompletely known. We investigated whether noradrenergic lesion modulates the levodopa (l-DOPA) response and modifies the response to adenosine antagonists and its interaction with l-DOPA. We examined the motor behaviour induced by: 1) subthreshold doses of l-DOPA (2mg/kg, i.p.), 2) the adenosine-receptor antagonist caffeine (10mg/kg), and 3) the combination of l-DOPA (2mg/kg) and caffeine (10mg/kg). Each study was done in two experimental conditions: a) rats with unilateral 6-OHDA lesion and b) rats with a lesion of the nigrostriatal pathway (6-OHDA) combined with selective denervation of locus coeruleus-noradrenergic terminal fields by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). While only 28% of the 6-OHDA-lesioned animals presented circling behaviour after l-DOPA challenge, all (100%) double-denervated animals rotated after the same l-DOPA dose (p<0.05). No statistical differences in the percentage of rotating animals were observed between single- and double-denervated rats after caffeine challenge. Combined l-DOPA-caffeine challenge produced rotational behaviour in all (100%) single- and double-denervated rats. No differences in total turns were observed between single- and double-denervated animals in each treatment condition. These findings suggest that additional noradrenergic denervation selectively decreases the motor threshold to l-DOPA treatment without modifying the magnitude or the pattern of the motor response to adenosinergic antagonism.
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PMID:Modulation of the motor response to dopaminergic drugs in a parkinsonian model of combined dopaminergic and noradrenergic degeneration. 1788 1

Adenosine and its receptors are, as part of the brain stress response, potential targets for neuroprotective drugs. We have investigated if the adenosine receptor system affects the developmental neurotoxicity caused by the fish pollutant methylmercury (MeHg). Behavioral outcomes of low dose perinatal MeHg exposure were studied in mice where the A(1) and A(2A) adenosine receptors were either partially blocked by caffeine treatment or eliminated by genetic modification (A(1)R and A(2A)R knock-out mice). From gestational day 7 to day 7 of lactation dams were administered doses that mimic human intake via normal diet, i.e. 1microM MeHg and/or 0.3g/l caffeine in the drinking water. This exposure to MeHg resulted in a doubling of brain Hg levels in wild type females and males at postnatal day 21 (PND21). Open field analysis was performed at PND21 and 2 months of age. MeHg caused time-dependent behavioral alterations preferentially in male mice. A decreased response to amphetamine in 2-month-old males pointed to disturbances in dopaminergic functions. Maternal caffeine intake induced long-lasting changes in the offspring evidenced by an increased motor activity and a modified response to psychostimulants in adult age, irrespectively of sex. Similar alterations were observed in A(1)R knock-out mice, suggesting that adenosine A(1) receptors are involved in the alterations triggered by caffeine exposure during development. Perinatal caffeine treatment and, to some extent, genetic elimination of adenosine A(1) receptors, attenuated the behavioral consequences of MeHg in males. Importantly, also deletion of the A(2A) adenosine receptor reduced the vulnerability to MeHg, consistent with the neuroprotective effects of adenosine A(2A) receptor inactivation observed in hypoxia and Parkinson's disease. Thus, the consequences of MeHg toxicity during gestation and lactation can be reduced by adenosine A(1) and A(2A) receptor inactivation, either via their genetic deletion or by treatment with their antagonist caffeine.
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PMID:The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration. 1792 Jan 82


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