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)

Interleukin (IL)-1 beta, IL-6, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) were measured for the first time in the brain (caudate nucleus, putamen and cerebral cortex) from control and parkinsonian patients by highly sensitive sandwich enzyme immunoassays. The concentrations of IL-1 beta, IL-6, EGF, and TGF-alpha in the dopaminergic, striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex did not show significant differences between parkinsonian and control subjects. Since these cytokines and growth factors may play important roles as neurotrophic factors in the brain, the present results suggest that they may be produced as compensatory responses in the nigrostriatal dopaminergic regions in Parkinson's disease, and may be related, at least in part, to the process of neurodegeneration in Parkinson's disease.
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PMID:Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. 770 May 68

Chronic inflammation associated with the amyloid plaques may represent an acute phase response in the brain. We quantitated the levels of two inflammatory markers; alpha 1-antichymotrypsin (alpha 1-ACT) and interleukin 1 beta (IL-1 beta) in paired serum and cerebrospinal fluid (CSF) samples from 40 patients with Alzheimer's disease (AD), 20 patients with Parkinson's disease (PD), and 42 age-matched controls. No differences in serum or CSF levels of either alpha 1-ACT or IL-1 beta were found between the groups. However, some AD patients had increased alpha 1-ACT index, suggesting an intrathecal production of alpha 1-ACT. Although alpha 1-ACT or IL-1 beta might be involved in the pathogenesis of AD, our results show that their measurement in serum or CSF is not valuable to support the clinical diagnosis of AD.
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PMID:Alpha 1-antichymotrypsin and IL-1 beta are not increased in CSF or serum in Alzheimer's disease. 793 55

Interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and interleukin-6 (IL-6) were measured in the cerebrospinal fluid (CSF) and plasma of 12 control subjects, 11 sporadic Alzheimer's disease (AD) and 22 de novo Parkinson's disease (PD) patients using high sensitivity enzyme-linked immunosorbent assays (ELISA). IL-1 beta and IL-6 contents were significantly elevated in the CSF of de novo PD and AD patients in comparison to the control group. In contrast, the plasma levels were not significantly affected. IL-2 contents in the CSF and plasma samples were unchanged in the three groups compared. Because the two cytokines IL-1 beta and IL-6 are known to play a key role in the interaction between the nervous and immune system, e.g. in the so-called acute phase response, our results support the involvement of immunological events in the complex process of neurodegeneration in AD and PD.
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PMID:Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. 878 20

Interleukin (IL)-1 beta , IL-2, IL-4, IL-6, epidermal growth factor (EGF), and transforming growth factor (TGF)-alpha were measured for the first time in ventricular cerebrospinal fluid (VCSF) from control non-parkinsonian patients, patients with juvenile parkinsonism (JP) and patients with Parkinson's disease (PD) by highly sensitive sandwich enzyme immunoassays. All cytokines were detectable in VCSF from control and parkinsonian patients, and the concentrations were much higher than those in lumbar CFS. The concentrations of IL-1 beta, IL-2, IL-4 and TGF-alpha in VCSF were higher in JP than those in controls (P < 0.05). In contrast, the concentrations of IL-2 and IL-6 in VCSF from patients with PD were higher than those from control patients (P < 0.05). These results agree with our previous reports, in which the cytokine levels were elevated in the striatal dopaminergic region of the brain from patients with PD. Since VCSF is produced in the ventricles, the alteration of cytokines in VCSF may reflect the changes of cytokines in the brain. Because cytokines play an important role as mitogens and neurotrophic factors in the brain, the increases in cytokines as a compensatory response may occur in the brain of patients of JP or PD during the progress of neurodegeneration. Increase in cytokines may contribute not only as a compensatory response but as a primary initiating trigger for the neurodegeneration.
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PMID:Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. 880 36

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to slow the progression of neurological deficits in PD and the cognitive decline in AD. The immune response to bacterial or viral infection and in chronic inflammatory processes is stimulated by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequently interleukin-6 (IL-6). We investigated the influence of Selegiline on the synthesis of IL-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) from healthy blood donors cultured with or without Selegiline (10(-8)M, 10(-9)M or 10(-10)M) in a humidified atmosphere (7% CO2). Treatment of cultured PBMC with Selegiline significantly increased synthesis of both cytokines. The effect of Selegiline on cytokine biosynthesis may contribute to its putative neuroprotective properties.
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PMID:Selegiline stimulates biosynthesis of cytokines interleukin-1 beta and interleukin-6. 911 94

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties.
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PMID:Selegiline as immunostimulant--a novel mechanism of action? 956 33

The capacity of peripheral blood mononuclear cells (PBMC) from patients with treated Parkinson's disease (PD) to produce interleukin (IL) IL-1 beta IL-2, IL-6, tumor necrosis factor (TNF)-alpha and the proliferative response to mitogens, was compared with that from cells from healthy subjects. The production of IL-2 and the mitogen response were significantly lower in PD patients, whereas the secretion of IL-1 beta, IL-6 and TNF-alpha were significantly enhanced. To evaluate the role of levodopa in creating immunological alterations, PBMC of patients and controls were incubated with concentrations of the drug extrapolated from those used in clinical practice. Levodopa caused an inhibition of mitogen-induced proliferation, stimulation of IL-6 and TNF-alpha production, whereas the secretion of IL-1 beta and IL-2 was not affected. The results of the study provide a further support for the interrelationship between the central nervous and immune system. In addition, the data indicate that the immunological alterations found in PD may be partially attributed to levodopa administration.
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PMID:IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease. 1034 2

We studied genetic polymorphisms in the promoter region (position -511) and exon 5 (position +3953) of the interleukin (IL)-1beta gene in 122 Japanese patients with Parkinson's disease (PD) and 112 controls. We also examined polymorphisms in the IL-1alpha and the IL-1 receptor antagonist genes. No significant difference was found in these genetic markers between PD patients and controls. However, PD patients with homozygotes for allele 1 at position -511 of the IL-1beta gene (IL-1B-511*1), a low producer of IL-1beta, were significantly earlier in the disease onset than those with the IL-1B-511*2 homozygotes, a high producer of IL-1beta. This suggests that IL-1beta might play a role, possibly a protective effect for dopaminergic neurons, in PD. Further population and functional studies are necessary to clarify the role of IL-1beta in PD patients.
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PMID:Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson's disease. 1077 Nov 65

Astrocytes, with their many functions in producing and controlling the environment in the brain, are of great interest when it comes to studying regeneration after injury and neurodegenerative diseases such as in grafting in Parkinson's disease. This study was performed to investigate astrocytic guidance of growth derived from dopaminergic neurons using organotypic cultures of rat fetal ventral mesencephalon. Primary cultures were studied at different time points starting from 3 days up to 28 days. Cultures were treated with either interleukin-1 beta (IL-1 beta), which has stimulating effects on astrocytic proliferation, or the astrocytic inhibitor cytosine arabinoside (Ara-C). Tyrosine hydroxylase (TH)-immunohistochemistry was used to visualize dopaminergic neurons, and antibodies against glial fibrillary acidic protein (GFAP) and S100 beta were used to label astrocytes. The results revealed that a robust TH-positive nerve fiber production was seen already at 3 days in vitro. These neurites had disappeared by 5 days. This early nerve fiber outgrowth was not guided by direct interactions with glial cells. Later, at 7 days in vitro, a second wave of TH-positive neuritic outgrowth was clearly observed. GFAP-positive astrocytic processes guided these neurites. TH-positive neurites arborized overlying S100 beta-positive astrocytes in an area distal to the GFAP-positive astrocytic processes. Treatment with IL-1 beta resulted in an increased area of TH-positive nerve fiber network. In cultures treated with Ara-C, neither astrocytes nor outgrowth of dopaminergic neurites were observed. In conclusion, this study shows that astrocytes play a major role in long-term dopaminergic outgrowth, both in axonal elongation and branching of neurites. The long-term nerve fiber growth is preceded by an early transient outgrowth of dopamine neurites.
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PMID:Guidance of dopaminergic neuritic growth by immature astrocytes in organotypic cultures of rat fetal ventral mesencephalon. 1180 34

Activated microglia surround degenerating substantia nigra neurons in Parkinson's disease (PD). Such microglia produce high levels of interleukin-1 beta (IL-1 beta) and interleukin-1 alpha (IL-1 alpha). T and C alleles exist for the IL-1 beta-511 regulatory region as well as for the IL-1 alpha-889 regulatory region. The T genotypes of both have been reported to increase the risk of Alzheimer's disease (AD) (Arch. Neurol. 58 (2001) 1790). Since the lesions of PD and AD have similar neuroinflammatory characteristics (Neurology 38 (1988) 1285), we genotyped 100 PD and 100 control postmortem brains for the same polymorphisms. We found a significant increase of the IL-1 beta T genotype in PD cases compared with controls (chi(2)=9.65, P=0.0019). A significant increase was not found for the IL-alpha T genotype (chi(2)=1.32, P=0.23), although there was a trend towards more frequent expression of the T allele.
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PMID:Association of interleukin-1 beta polymorphisms with idiopathic Parkinson's disease. 1205 40


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