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)

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by the selective loss of dopaminergic neurons of the nigrostriatal pathway. Epidemiological studies have shown an inverse relationship between coffee consumption and susceptibility to PD. Cytochrome P450 1A2 (CYP1A2) is involved in caffeine metabolism and its clearance. Caffeine, on the other hand, antagonizes adenosine A(2A) receptor and regulates dopamine signaling through dopamine transporter (DAT). The present study was undertaken to investigate the expression of CYP1A2, adenosine A(2A) receptor and DAT in mouse striatum and to assess their levels in 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropryridine (MPTP) treated mouse striatum with and without caffeine treatment. The animals were treated intraperitoneally daily with caffeine (20 mg/kg) for 8 weeks, followed by MPTP (20 mg/kg)+caffeine (20 mg/kg) for 4 weeks or vice versa, along with respective controls. Tyrosine hydroxylase immunoreactivity, levels of dopamine and 1-methyl 4-phenylpyridinium ion (MPP(+)), expressions of CYP1A2, adenosine A(2A) receptor and DAT and CYP1A2 catalytic activity were measured in control and treated mouse brain. Caffeine partially protected MPTP-induced neurodegenerative changes and modulated MPTP-mediated alterations in the expression and catalytic activity of CYP1A2, expression of adenosine A(2A) receptor and DAT. The results demonstrate that caffeine alters the striatal CYP1A2, adenosine A(2A) receptor and DAT expressions in mice exposed to MPTP.
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PMID:Effect of caffeine on the expression of cytochrome P450 1A2, adenosine A2A receptor and dopamine transporter in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine treated mouse striatum. 1952 64

Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson's disease. Here we assessed whether chronic caffeine treatment increases the resistance of male Wistar rats to haloperidol (1mg/kg, s.c.)-induced catalepsy, measured in the bar test at 15 min intervals during 3h. Caffeine (5mg/kg/day) was delivered for 6 months via drinking water. Control rats received only tap water. Treatments began when animals were 3-4 months old. In order to unveil long-lasting catalepsy refractoriness not attributable to the presence of caffeine in the brains of rats, they were evaluated from day 18 to day 27 after caffeine withdrawal, a time that is far in excess for the full excretion of a caffeine dose in this species. The average cataleptic immobility measured in caffeine-treated rats (n=23) was 1148+/-140 s, a value 34+/-8% lower than that recorded in control animals (n=20), whose mean immobility was 1736+/-137 s (P=0.0026, t-test). The percentage of catalepsy reduction measured in caffeine-treated rats evaluated on days 18-20 after caffeine discontinuation (-32+/-13%, n=12, P<0.05) was comparable to the catalepsy decrease recorded in those animals tested on days 21-27 (-36+/-10%, n=11, P<0.02), a finding compatible with the notion that the effect was indeed mediated by enduring changes of brain functioning and not by the physical presence of caffeine or its metabolites. Caffeine-treated rats also had higher catalepsy latency scores compared with control rats (P<0.01, U-test). The present findings show that chronic consumption of caffeine produces perdurable resistance to catalepsy induced by dopamine receptor blockade, possibly through enhancement of dopamine transmission, giving further support to the epidemiological results indicating that prolonged caffeine consumption affords neuroprotection against Parkinson's disease.
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PMID:Long-lasting resistance to haloperidol-induced catalepsy in male rats chronically treated with caffeine. 1965 37

Nearly two-thirds of patients with Parkinson's disease (PD) use vitamins or nutritional supplements, and many more may use other complementary therapies, yet <50% of patients have discussed the use of these complementary therapies with a healthcare professional. Physicians should be aware of the complementary therapies their patients with PD are using, and the possible effects of these therapies on motor and non-motor symptoms. Complementary therapies, such as altered diet, dietary supplements, vitamin therapy, herbal supplements, caffeine, nicotine, exercise, physical therapy, massage therapy, melatonin, bright-light therapy and acupuncture, may all influence the symptoms of PD and/or the effectiveness of dopaminergic therapy. Preliminary evidence suggests complementary therapy also may influence non-motor symptoms of PD, such as respiratory disorders, gastrointestinal disorders, mood disorders, sleep and orthostatic hypotension. Whenever possible, clinicians should ensure that complementary therapy is used appropriately in PD patients without reducing the benefits of dopaminergic therapy.
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PMID:Potential influences of complementary therapy on motor and non-motor complications in Parkinson's disease. 1973 93

Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.
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PMID:Caffeine and adenosine. 2016 66

Sporadic Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases and as such they represent major public health problems. Finding effective treatments for AD and PD represents an unmet and elusive goal largely because these diseases are chronic and progressive, and have a complicated and ill-understood pathogenesis. Although the underlying mechanisms are not fully understood, caffeine, the most commonly ingested psychoactive drug in the world, has been shown in human and animal studies to be protective against AD and PD. One mechanism implicated in the pathogenesis of AD and PD is blood-brain barrier (BBB) dysfunction and we reported recently that caffeine exerts protective effects against AD and PD at least in part by keeping the BBB intact. The present review focuses on the role of BBB dysfunction in the pathogenesis of AD and PD, caffeine's protective effects against AD and PD, and potential mechanisms whereby caffeine protects against BBB leakage.
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PMID:Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's diseases. 2016 68

Epidemiological studies have raised the possibility of caffeine serving as a neuroprotective agent in Parkinson's disease (PD). This possibility has gained support from findings that dopaminergic neuron toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or other neurotoxins is attenuated by co-administration of caffeine in mice. Here we examined the time window of caffeine's neuroprotection as well as the effects of caffeine's metabolites (theophylline and paraxanthine) in the MPTP mouse model of PD. In the first experiment, caffeine pre-treatment (30 mg/kg ip) significantly attenuated MPTP-induced striatal dopamine depletion when it was given 10 min, 30 min, 1 h, or 2 h but not 6 h before MPTP (40 mg/kg ip) treatment. Meanwhile, caffeine post-treatment also significantly attenuated striatal dopamine loss when it was given 10 min, 30 min, 1 h or 2 h but not 4 h, 8 h or 24 h after MPTP injection. In the second experiment, both theophylline (10 or 20 mg/kg) and paraxanthine (10 or 30 mg/kg) administration (10 min before MPTP) significantly attenuated MPTP-induced dopamine depletion in mice, as did caffeine (10 mg/kg) treatment. Thus the metabolites of caffeine also provide neuroprotective effects in this mouse model of PD. The data suggest that if caffeine protects against putative toxin-induced dopaminergic neuron injury in humans, then precise temporal pairing between caffeine and toxin exposures may not be critical because the duration of neuroprotection by caffeine may be extended by protective effects of its major metabolites.
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PMID:Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson's disease. 2016 58

Several studies conducted worldwide report an inverse association between caffeine/coffee consumption and the risk of developing Parkinson's disease (PD). However, heterogeneity and conflicting results between studies preclude a correct estimation of the strength of this association. We conducted a systematic review and meta-analysis of published epidemiological studies to better estimate the effect of caffeine exposure on the incidence of PD. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort, case-control and cross-sectional studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Twenty-six studies were included: 7 cohort, 2 nested case-control, 16 case-control, and 1 cross-sectional study. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The summary RR for the association between caffeine intake and PD was 0.75 [[95% Confidence Interval (95%CI): 0.68-0.82], with low to moderate heterogeneity (I2= 28.8%). Publication bias for case-control/cross-sectional studies may exist (Egger's test, p=0.053). When considering only the cohort studies, the RR was 0.80 (95%CI: 0.71-90; I2=8.1%). The negative association was weaker when only women were considered (RR=0.86, 95%CI: 0.73-1.02; I2=12.9%). A linear relation was observed between levels of exposure to caffeine and the RR estimates: RR of 0.76 (95%CI: 0.72-0.80; I2= 35.1%) per 300 mg increase in caffeine intake. This study confirm an inverse association between caffeine intake and the risk of PD, which can hardly by explained by bias or uncontrolled confounding.
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PMID:Caffeine exposure and the risk of Parkinson's disease: a systematic review and meta-analysis of observational studies. 2018 23

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs (rigidity, bradykinesia, rest tremor) that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta. Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms in PD. The present review attempts to examine results reported in epidemiological, clinical and animal studies to provide a comprehensive picture of the antiparkinsonian potential of caffeine. Convergent epidemiological and pre-clinical data suggest that caffeine may confer neuroprotection against the underlying dopaminergic neuron degeneration, and influence the onset and progression of PD. The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. Finally, recent experimental findings have indicated the potential of caffeine in the management of non-motor symptoms of PD, which do not improve with the current dopaminergic drugs. Altogether, the studies reviewed provide strong evidence that caffeine may represent a promising therapeutic tool in PD, thus being the first compound to restore both motor and non-motor early symptoms of PD together with its neuroprotective potential.
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PMID:Effects of caffeine in Parkinson's disease: from neuroprotection to the management of motor and non-motor symptoms. 2018 24

Caffeine, the most widely consumed psychoactive drug, enhances attention/vigilance, stabilizes mood, and might also independently enhance cognitive performance. Notably, caffeine displays clearer and more robust beneficial effects on memory performance when memory is perturbed by stressful or noxious stimuli either in human or animal studies. Thus, caffeine restores memory performance in sleep-deprived or aged human individuals, a finding replicated in rodent animal models. Likewise, in animal models of Alzheimer's disease (AD), caffeine alleviates memory dysfunction, which is in accordance with the tentative inverse correlation between caffeine intake and the incidence of AD in different (but not all) cohorts. Caffeine also affords beneficial effects in animal models of conditions expected to impair memory performance such as Parkinson's disease, chronic stress, type 2 diabetes, attention deficit and hyperactivity disorder, early life convulsions, or alcohol-induced amnesia. Thus, caffeine should not be viewed as a cognitive enhancer but instead as a cognitive normalizer. Interestingly, these beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2A receptors. This prominent role of A2A receptors in preventing memory deterioration is probably related to the synaptic localization of this receptor in limbic areas and its ability to control glutamatergic transmission, especially NMDA receptor-dependent plasticity, and to control apoptosis, brain metabolism, and the burden of neuroinflammation. This opens the real and exciting possibility that caffeine consumption might be a prophylactic strategy and A2A receptor antagonists may be a novel therapeutic option to manage memory dysfunction both in AD and in other chronic neurodegenerative disorders where memory deficits occur.
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PMID:Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline. 2018 43

Many people with Parkinson's disease (PD) and their family members ask their physicians "What is happening in research on Parkinson's disease? Is there anything new?" As the initial speaker at the symposium organized by the Parkinson's Disease Foundation in celebration of its 50th anniversary, I sought to address these questions, focusing on research published between the years 1997 and 2007. I cataloged the advances I considered most important in the field, recognizing my viewpoint is a subjective one and most likely differs from similar listings that others would put together. Space limitation allows me to discuss only a tiny fraction of the remarkable new findings that have been discovered during this 10-year span. Nevertheless, I expect the readers of this summation of advances in the field to be as impressed as I am on the wealth, breadth, and excitement stirring in the field of PD research. Included in this overview are highlights in both laboratory science and clinical science of PD research. In the former category are advances in knowledge on the genetics of PD; potential etiologic and pathogenic causes, especially the better understanding of endogenous factors within dopaminergic neurons; pathologic changes including deposition of alpha-synuclein aggregates; and the consequences of altered alpha-synuclein on the degradation of proteins by both the ubiquitin-proteasomal pathway and the lysosome. Clinical science has also been very active and impressively productive with important clinical advances. In this category are new information on the epidemiology of PD, including awareness of additional factors (besides smoking) that might slow the onset and worsening of PD, such as caffeine and urate; neuroimaging with positron emission tomography and single photon emission tomography; keener awareness of nonmotor features of PD and their impact on quality of life for the persons with PD and their family; recognition of behavioral complications of medications utilized to treat PD, such as impulse control problems; appreciation of the natural history of PD with the increasing impairments as the disease relentlessly worsens over time; the many controlled clinical trials attempting to slow the progression of the disease and to provide new symptomatic therapies; and surgical approaches to alleviate symptoms and progression, including cellular and gene therapy as well as deep brain stimulation.
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PMID:Parkinson's disease: 10 years of progress, 1997-2007. 2018 39


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