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)

The localization of adrenergic receptors in the central nervous system was studied in two physiological conditions of noradrenergic denervation, a 6-hydroxydopamine-induced lesion of the locus coeruleus in newborn rat, and a pathological related degeneration of the locus coeruleus in man, Parkinson's disease. The localization of these receptors in the synapse has been studied with the technique of subcellular fractionation by differential centrifugation. In lesioned rats, an increase in the density of alpha 1 and beta 1 receptors was observed in several brain regions, in contrast to alpha 2 receptors which were not modified. Subcellular fractionation in lesioned rats showed an increase in alpha 1 and beta 1 receptors in synaptosomal fractions. Similar results were found in parkinsonian patients: alpha 1 receptors increased in the synaptosomal fraction; beta receptors increased in synaptosomal and microsomal fractions. These results suggest that alpha 1 and beta 1 receptors may be located on non-noradrenergic nerve terminals in mammalian brain. alpha 2 and beta 2 receptors may be situated on glial cells or neuronal elements unrelated to noradrenergic input.
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PMID:Cellular localization of adrenergic receptors in rat and human brain. 308 66

Transforming growth factor (TGF)-beta 1 content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) and in ventricular cerebrospinal fluid (VCSF) from control and parkinsonian patients by a sandwich enzyme immunoassay. The concentrations of TGF-beta 1 were significantly higher in the dopaminergic striatal regions in parkinsonian patients than those in controls, but were not significantly different in the cerebral cortex between parkinsonian and control patients. Furthermore, the concentrations of TGF-beta 1 in VCSF were significantly higher in parkinsonian patients than those in non-parkinsonian control patients. Since TGF-beta 1 has potent regulatory activity on cell growth, these results suggest that TGF-beta 1 may have some significant modulatory role in the process of neurodegeneration in Parkinson's disease.
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PMID:Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease. 747 58

It has been believed that patients with neurogenic orthostatic hypotension (NOH) usually develop denervation supersensitivity of cardiovascular alpha-, beta 1- and beta 2-adrenoceptors, because the majority studies have shown augmented cardiovascular responses to intravenously given noradrenaline (NA) or isoprenaline (IP) in these patients. This view, however, leaves room for discussion. First, drugs were administered by means of drip infusion method in most of the previous studies. Since this method necessarily provokes baroreflex, which is buffering fluctuations in blood pressure and heart rate, the results may reflect diminished baroreflex rather than denervation supersensitivity. Second, adrenoceptor functions are modulated by multiple factors, such as ageing, thyroid hormone and chronic inflammation. It is, thus, inappropriate to explain the whole picture of functional change in adrenoceptors by the denervation mechanism only. In order to look over the cardiovascular adrenoceptor functions in NOH, we performed bolus infusion tests of NA and IP on the patients. The subjects comprised 7 cases of NOH with pre-ganglionic sympathetic deficit (NOH-I), 6 cases with post-ganglionic deficit (NOH-II) and 15 healthy controls. NOH-I group included 6 patients with multiple system atrophy and one with Parkinson disease, while NOH-II group consisted of 3 patients with idiopathic orthostatic hypotension (pure autonomic failure) and 3 with diabetic autonomic neuropathy. Both NA and IP infusion tests were carried out under the continuous measurement of blood pressure and heart rate. In NA test, different bolus doses (0.01, 0.02, 0.05 and 0.1 microgram/kg) of NA were intravenously administered, and a degree of subsequent rise in mean blood pressure was used as an index for alpha-adrenoceptor function. IP test was performed in the same manner, and an increase in heart rate and a fall in mean blood pressure in response to the drug (0.001, 0.002 and 0.005 microgram/kg) were measured as indices for beta 1- and beta 2-functions, respectively. A rise in blood pressure following the administration of any dose of NA did not statistically differ among three groups. An increase in heart rate in IP test was generally lower in both NOH groups, and a significant difference was obtained between NOH-I and control when a given dose was 0.005 microgram/kg) (p < 0.02). A fall in blood pressure in IP test was significantly greater in NOH-I compared to control when doses were 0.002 and 0.005 microgram/kg (p < 0.02 and 0.01, respectively). It was also greater in NOH-II than in control when a dose was 0.002 microgram/kg (p < 0.01). In disagreement with most of the previous studies, the present results suggest that alpha-adrenoceptor function is hardly altered, beta 1-function is suppressed, and beta 2-function is augmented in NOH.
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PMID:[Cardiovascular alpha-, beta 1- and beta 2-adrenoceptor functions in neurogenic orthostatic hypotension]. 882 96

Recently several responsible genes for hereditary neurodegenerative disorders were identified. In some of them the gene products were found to be aggregated. In the case of Alzheimer disease beta protein and apolipoprotein E accumulated in senile plaques. In CAG repeat diseases the polyglutamine aggregates in neuronal nuclei. More recently alpha synuclein accumulates in Lewy bodies in Parkinson disease and tau protein accumulates in NFT of hereditary frontotemporal dementia with tau mutation. Those results suggested that the responsible gene products accumulates in the lesion which the products involve in. However, presenilin which is one of the genes for familial Alzheimer disease accumulates in NFT and on the other hand its mutation changes the production ratio of beta 1-42/40, suggesting that the abnormal gene products not simply accumulate the lesion that it involved. The gene products accumulate in different lesions such as in nuclei of polyglutamine diseases, extracellular plaque and cytoplasm of prion disease and extracellular plaques in Alzheimer disease. Some of them are ubiquitinated and some of them are not. Thus the accumulating process in these disorders seems apparently same but is essentially different. We should study more precisely each pathological process of those disorders.
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PMID:[Neuronal cell death--what we can see and what we cannot]. 1037 83

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.
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PMID:N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation. 1114 96

Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most frequent cause of dementia in the elderly. The identification of activated microglia within neuritic plaques, coupled with the presence of numerous inflammatory proteins, suggests that inflammation is an integral part of the pathogenetic process in AD. In the present paper we have investigated the levels of circulating inflammatory mediators as potential AD biomarkers concentrating essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor receptor superfamily lacking the membrane-associated endodomain by alternative splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD patients could enhance the effects of pro-inflammatory cytokines produced by activated microglia as well as the expression of factors, such as the CD40/CD40 ligand complex, by microglia and astrocytes. Total venous blood samples were obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40 healthy age-matched and 11 healthy young individuals. A significant increase of sCD40 levels plasma of AD patients versus healthy controls was measured, concomitantly with a decrease in TGF-beta1 concentration. These variations, however, showed no correlation with the expression of ApoE epsilon 4 allele, which was determined in order to assess the different frequency of this risk factor between AD and control groups. Since no comparable modifications were detected in patients affected by Parkinson's disease or non-AD-based dementia, we propose that sCD40 and TGF-beta1 plasma levels might represent possible differential biomarkers of AD, and be useful pre-mortem to support the clinical diagnosis of late-onset AD.
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PMID:Increased plasma levels of soluble CD40, together with the decrease of TGF beta 1, as possible differential markers of Alzheimer disease. 1550 Oct 26

This study examined sensorimotor integration and motor functioning in seven patients with Parkinson's disease (PD) who had mild symptoms, and seven age-matched controls. Neuro-oscillations were recorded by high-density 128-channel electroencephalography (EEG). Participants were required to perform two tasks: simple tapping of the index finger and thumb and a complex Luria finger apposition task. Both tasks were performed unimanually and bimanually. There were no significant group differences in the task-related power (TRPow) within alpha 1 (mu1) or in beta 1 frequencies (beta1). In contrast, there were significant group differences in the alpha 2 (mu2) and beta 2 frequencies (beta2). Patients had less desychronisation than controls at the electrodes covering the central regions of the scalp. Alpha 2 and beta 2 frequencies have been associated with task-specific sensorimotor integration and motor function, respectively. This activity difference in patients with Parkinson's disease may be due to deficits in sensorimotor integration.
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PMID:Decreased desychronisation during self-paced movements in frequency bands involving sensorimotor integration and motor functioning in Parkinson's disease. 1711 53

Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.
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PMID:Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity. 1829 64

Neurological symptoms of patients suffering from neurodegenerative diseases such as Alzheimer's dementia (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) often worsen during infections. We assessed the disease-modulating effects of recurrent systemic infections with the most frequent respiratory pathogen, Streptococcus pneumoniae, on the course of AD, PD, and ALS in mouse models of these neurodegenerative diseases [transgenic Tg2576 mice, (Thy1)-[A30P]alpha SYN mice, and Tg(SOD1-G93A) mice]. Mice were repeatedly challenged intraperitoneally with live S. pneumoniae type 3 and treated with ceftriaxone for 3 days. Infection caused an increase of interleukin-6 concentrations in brain homogenates. The clinical status of (Thy1)-[A30P]alpha SYN mice and Tg(SOD1-G93A) mice was monitored by repeated assessment with a clinical score. Motor performance was controlled by the tightrope test and the rotarod test. In Tg2576 mice, spatial memory and learning deficits were assessed in the Morris water maze. In none of the three mouse models onset or course of the disease as evaluated by the clinical tests was affected by the recurrent systemic infections performed. Levels of alpha-synuclein in brains of (Thy1)-[A30P]alpha SYN mice did not differ between infected animals and control animals. Plaque sizes and concentrations of A beta 1-40 and A beta 1-42 were not significantly different in brains of infected and uninfected Tg2576 mice. In conclusion, onset and course of disease in mouse models of three common neurodegenerative disorders were not influenced by repeated systemic infections with S. pneumoniae, indicating that the effect of moderately severe acute infections on the course of neurodegenerative diseases may be less pronounced than suspected.
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PMID:Recurrent systemic infections with Streptococcus pneumoniae do not aggravate the course of experimental neurodegenerative diseases. 1985 62

The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to Alzheimer's disease dementia (ADD), Parkinson's disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini-Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.
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PMID:Abnormalities of cortical neural synchronization mechanisms in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study. 2845 45


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