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)

Normal brain aging is accompanied by the losses of certain neuronal populations and the appearance of structures such as neuronal plaques and neurofibrillary tangles. Additionally, various neurotransmitter systems are altered in the elderly, although marked variations are observed between individuals, suggesting important differences between successful and unsuccessful aging. In certain pathological conditions, only certain features of normal aging are exacerbated. For example, the densities of forebrain cholinergic neurons are markedly decreased in cortical and hippocampal (but not striatal) areas in Alzheimer's disease. We discuss here the comparative alterations of cholinergic markers in certain neurological disorders such as Alzheimer's disease, Parkinson's disease, and the combined pathology. Differential alterations of brain cholinergic profile are observed in each disorder, this most likely having functional significance. We also found that muscarinic receptors of the M2 subtype act as negative autoreceptors to decrease brain acetylcholine release, whereas nicotinic agonists induced the opposite effect. This suggests that blockade of negative M2 or stimulation of positive nicotinic autoreceptors could have beneficial effects in Alzheimer's disease. Additionally, modulation of heteroreceptor activation such as the serotonergic or interleukin-2 sites located on or in proximity to cholinergic nerve terminals could offer alternate strategies for the treatment of cholinergic deficits in pathological brain aging.
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PMID:Neurochemical deficits in pathological brain aging: specificity and possible relevance for treatment strategies. 209 19

The present study determined whether molecules normally associated with immune signalling processes, specifically the lymphokines interleukin-1 beta, -2, -3 and -6, can be detected in the human hippocampal formation, and whether their levels are altered in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Interleukin-1 beta, -2, -3 and -6 were measured in post mortem tissues from 14 control neurologically normal subjects, 24 patients with Alzheimer's disease and 17 patients with Parkinson's disease. In order to assess the extent of the cholinergic deficit in the Alzheimer's disease brains, choline acetyltransferase activity in the hippocampal formation was first determined. In the Alzheimer's disease tissues, choline acetyltransferase activity was significantly reduced (by 58%) compared to the control hippocampi, whereas that in the Parkinson's disease hippocampi was not significantly different from control. Using radioimmunoassays with antisera specific for the respective interleukin, marked increases in the content of immunoreactive interleukin-1 beta (99%), interleukin-2 (129%) and interleukin-3 (64%) could be detected in the Alzheimer's, but not the Parkinson's disease hippocampi. Interleukin-6 levels were not significantly different in either group, compared to the control hippocampi. Since striking elevations in various interleukins were detected in the Alzheimer's disease hippocampi, the possibility that concomitant alterations in interleukin receptor sites also occurred was investigated. Using radioligand binding to hippocampal membranes, low levels of interleukin binding were measured in the control hippocampi. In the Alzheimer's tissues, significant elevations in [125I]interleukin-1 beta (by 65%) and [125I]interleukin-2 (by 69%) binding were noted. In contrast, [125I]interleukin-3 binding was not different in the Alzheimer's disease compared to the control tissues. In the hippocampal formation of Parkinson's disease brains, only [125I]interleukin-2 binding was significantly increased (by 80%). In summary, the present results indicate that there is pronounced activation of immune system function, particularly specific immune mediators such as the interleukins, in the hippocampal formation in Alzheimer's disease, and further suggest that stimulation of immune function may be an integral component of the pathological changes that occur in this disease.
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PMID:Induction of immune system mediators in the hippocampal formation in Alzheimer's and Parkinson's diseases: selective effects on specific interleukins and interleukin receptors. 783 74

Adenosine deaminase (ADA) and its isozyme activities in serum were measured together with peripheral lymphocyte subsets in 42 patients with idiopathic Parkinson's disease. The total and ADA 2 activities were significantly higher than normal controls (p < 0.01). As regards the peripheral lymphocyte subsets, the proportion of OKT 10+ cells (activated T lymphocytes) and the proportions of interleukin-2 receptor+ and HLA-DR+ cells (mainly activated T lymphocytes) were significantly higher than normal controls (p < 0.05, 0.01, 0.01, respectively). On the other hand, OKT 10+ cells demonstrated a significant correlation not only with total ADA but also with ADA 2 activity. These results suggest that high serum ADA activity may be involved in the pathogenesis of Parkinson's disease through peripheral T lymphocyte activation.
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PMID:A correlation study between serum adenosine deaminase activities and peripheral lymphocyte subsets in Parkinson's disease. 854 43

The pathogenesis of Parkinson's disease (PD) is largely unknown. Recently, several studies have presented evidence of an immunological dysfunction in patients suffering from PD. We studied the immune responsiveness of patients with idiopathic PD (n = 20) by investigation of the ability of peripheral blood mononuclear cells to produce cytokines after mitogenic stimulation in a whole blood assay. A group of age-related healthy blood donors served as control (n = 19). Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. PD patients had a significantly higher neutrophil count, but analysis of T-cell subsets showed no difference between the two groups. In peripheral blood, secretion of interleukin-2 (IL-2) after mitogenic stimulation was significantly diminished in the patients' group (p < 0.01), whereas values of IFN-alpha 2, IL-6, IFN-gamma and sIL-2R were comparable in both groups. IL-2 production correlated negatively with the mean annual dose of levodopa treatment and correlated significantly (p < 0.002) with amantadine uptake. Analysis of sex, age, duration of illness and other drug intake revealed no correlation with cytokine release. Our findings support the view that there is a selective abnormality in the immune repertoire of peripheral blood lymphocytes in patients suffering from PD, the reasons for which need to be explored.
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PMID:Defective production of interleukin-2 in patients with idiopathic Parkinson's disease. 858 16

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

Parkinson's disease (PD) is characterized by a markedly decreased number of nigrostriatal dopaminergic neurons. The pathogenesis of PD is still unknown; among other etiological factors, immunological abnormalities have been suggested. Recently, interleukin-2 (IL-2) has been hypothesized to be an endogenous cytokine that regulates striatal dopaminergic function. We examined the plasma concentrations of IL-1, IL-2, IL-6 and blood levels of ACTH, cortisol and prolactin of 21 patients with PD without any previous treatment. Age- and sex-matched subjects without any neurological or immune disorders were used as controls. Significantly higher serum concentrations of IL-2 in patients with PD were found. Treatment with antiparkinsonian drugs reduced IL-2 levels in these patients. Our results suggested a functional relationship between central dopaminergic and immune systems and a possible involvement of the latter in the pathogenesis of PD.
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PMID:Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson's disease. 894 28

Interleukin-2 (IL-2) has recently been implicated as a modulator of brain neuronal function and in the pathogenesis of several major neuropsychiatric disorders involving the dopamine system (e.g. schizophrenia and Parkinson's disease). Little is known, however, about the effects of IL-2 on dopamine-mediated behaviors. A series of behavioral experiments were performed in mice to examine the hypothesis that species-specific IL-2 could modify behaviors known to be mediated by forebrain dopamine pathways. IL-2 administered subcutaneously produced a robust increase in locomotor activity in an elevated plus-maze. No effects of the cytokine were evident on measures of acoustic startle, prepulse inhibition of the startle response (PPI), or fearfulness. In complementary in vitro neurochemical experiments, to most closely assess physiologically relevant effects of the cytokine on dopamine release from striatal neurons, species-specific IL-2 as well as high performance liquid chromatography (HPLC) were used to measure endogenous dopamine release from striatal slices. IL-2 dose-dependently modulated veratrine-evoked release of endogenous dopamine in a biphasic pattern, increasing release at lower concentrations and inhibiting release at a high concentration of the cytokine. In radioligand competition binding experiments, IL-2 was not active at striatal binding sites for [3H]spiroperidol (D2-like receptors), [3H]mazindol binding (dopamine uptake sites) and [3H]SCH23390 (D1-like receptors), indicating that the neuromodulatory actions of IL-2 are not the result of direct or allosteric effects on dopamine receptors. Knowledge of the mechanisms by which IL-2 influences brain dopamine function could provide new insight into the pathophysiology of forebrain dopamine neurons seen in disorders such as Parkinson's disease and schizophrenia.
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PMID:Modulation of behavioral and neurochemical measures of forebrain dopamine function in mice by species-specific interleukin-2. 905 75

Allogeneic transplantation for the therapy of human Parkinson's disease is being considered as a viable approach at several clinical centers worldwide. As an attempt to understand the basic biology of central nervous system (CNS) transplantation, our laboratory has developed an experimental nonhuman primate model for human Parkinson's disease and carried out preliminary studies directed at evaluating the potential pathology at the graft site. In addition, studies have been conducted to examine whether such transplantation procedures lead to specific and/or nonspecific immunologic sensitization of the host or results in generalized immunosuppression. Groups of rhesus macaques (Macaca mulatta) were either controls operated (n = 6), autografted with adrenal medullary and peripheral nerve tissue (n = 3), or allografted with fetal mesencephalic tissue (n = 6). Immunohistological studies demonstrated the presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cells declined with time. The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+. There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto- or allografts. Tissue sections obtained postoperatively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in neural tissue. A small aliquot of tissue from the operative site was placed in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells. Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto- and allograft recipient monkeys performed at varying time periods postoperatively failed to show differences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes. Studies on aliquots of the same PBMC failed to show major functional differences in NK-cells, LAK cells, or response to polyclonal mitogens. Finally, recipients of allogeneic mesencephalic grafts failed to show evidence of donor-specific humoral or cellular sensitization. These data indicate that transplantation of autograft adrenal or allograft fetal mesencephalic tissues in the CNS of nonhuman primate did not induce detectable donor-specific sensitization nor nonspecific immunosuppression.
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PMID:Immunological responses to injury and grafting in the central nervous system of nonhuman primates. 958 93

An involvement of immunological events in the process of neurodegeneration has frequently been reported. We investigated the cytokine producing capacity for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in whole blood cultures of de-novo patients with idiopathic Parkinson's disease (PD) at the time of first diagnosis and after oral amantadine treatment. Before treatment, productions of IL-2 and IFN-gamma were markedly decreased in PD patients compared to patients with major depressive disorder and healthy controls. After amantadine treatment, the in vitro IL-2 secretion defect was corrected to normal levels in half of the patients, and the increase in IL-2 production was correlated with an increase in IFN-gamma secretion. Our findings suggest that immunological abnormalities occur in the course of PD and that a formerly unappreciated therapeutic potential of amantadine may arise from its immunomodulatory effects on altered T cell function in patients with PD.
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PMID:Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson's disease. 1043 55

Animal models of Parkinson's disease with dementia would greatly facilitate research into the underlying causes of this disorder. Here, we showed that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, cell loss in the hippocampal CA1 area, as well as microglial activation and increase of interleukin-2 levels in several brain regions. In addition, increase of anxiety-like behavior and impairment of object recognition were observed in the MPTP-lesioned rats. These findings suggest that neuroinflammation may contribute to MPTP-induced neurodegeneration and behavioral deficits, which is suggested as an animal model of Parkinson's disease dementia.
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PMID:MPTP lesion causes neuroinflammation and deficits in object recognition in Wistar rats. 2000 Nov 9


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