Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of pale bodies and Lewy bodies was studied in the substantia nigra of 12 patients with typical Parkinson's disease (PD), in 5 patients with diffuse Lewy body disease (DLBD), and in a group of neurologically normal controls. Anti-ubiquitin antibodies labelled pale bodies and Lewy bodies in typical PD and DLBD, and there was a strong positive correlation between numbers of ubiquitin-immunoreactive pale bodies and Lewy bodies. BF10, a monoclonal antibody against a phosphate-dependent epitope of neurofilament 155-kDa polypeptide subunit, immunolabelled 57% of Lewy bodies and 15% of pale bodies in typical PD. Some pale bodies and Lewy bodies were seen in the substantia nigra of 2 of 5 neurologically normal, aged controls, probably representing "incidental PD". We conclude that there is a close relationship between pale bodies and typical Lewy bodies in the substantia nigra in clinical varieties of PD, and that these inclusions share antigenic determinants. If pale bodies and Lewy bodies reflect separate aspects of the cellular pathology in PD, their formation probably occurs in parallel. Alternatively, these observations may suggest that pale bodies represent a stage in the formation of Lewy bodies.
 ...
PMID:Relationships between Lewy bodies and pale bodies in Parkinson's disease. 132 Mar 23

Lewy bodies are cytoskeletal inclusions associated with neuronal injury and death in idiopathic Parkinson's disease and other neurodegenerative disorders. The chemical composition of the 8-10-nm fibrils of the Lewy body is unknown, although they are related to both normal cytoskeletal elements and paired helical filaments of Alzheimer neurofibrillary tangles. From the Lewy body-rich cerebral cortex of patients with diffuse Lewy body disease we have isolated intact Lewy bodies using a high salt buffer/nonionic detergent gradient centrifugation procedure and extracted the constitutive fibrils with urea and sodium dodecyl sulfate. Urea/detergent-resistant Lewy body fibrils were solubilized with formic acid and found to contain a single protein band of 68 kDa, which was not found in identically prepared normal brain homogenates. The Lewy body derived-polypeptide was recognized on immunoblots by a polyclonal antibody that reacted with both the 68-kDa neurofilament subunit and the microtubule-associated protein tau. The 68-kDa Lewy body protein was not labeled by the monoclonal antibody tau-1 despite prior in vitro enzymatic dephosphorylation. We conclude that the detergent-insoluble component of the cortical Lewy body fibril shares epitopes with neurofilament and tau and may be a posttranslationally modified derivative of either neurofilament or tau with substantially altered biochemical and immunologic properties.
 ...
PMID:Detergent-insoluble cortical Lewy body fibrils share epitopes with neurofilament and tau. 137 81

The concentrations of somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), beta-endorphin (beta-EP), adrenocorticotropin (ACTH) and corticotropin-releasing factor (CRF) immunoreactivity were measured in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), patients with Parkinson's disease (PD) and controls. In order to study the mechanisms that regulate peptide levels in CSF and peptide interactions, correlations between CSF peptides were determined. Within all patient groups a number of significant correlations were shown to exist between CSF peptides. The correlations were apparently not coincidental, since there was no such relation between the concentrations of CSF peptides and CSF protein content. Neither age, sex, severity of dementia nor the presence of extrapyramidal signs could explain the number of significant correlations. These results indicate, that the correlations found between CSF peptides may be due to common regulatory mechanisms or general physiological behaviour of peptides in the CSF.
 ...
PMID:A correlation study of CSF neuropeptides in Alzheimer's and Parkinson's disease. 168 48

We performed immunohistochemical analysis of specimens from three autopsied patients with Parkinson's disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinson's disease.
 ...
PMID:Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. 197 53

Energy expenditure was determined in 18 patients with Parkinson's disease, 6 healthy volunteers and 6 patients with essential tremor, age-matched, using the indirect calorimetric method which measures the gas exchange rate. The results showed a significant increase in the relative energy expenditure, i.e. the difference between absolute and predictable values from the Harris and Benedict equation, among the parkinsonian patients (+21 +/- 4.1 p. 100; mean +/- S.E.M.) as compared to the 2 control groups (-8.6 +/- 7 p. 100 and -2.1 +/- 4.1 p. 100 respectively; p less than 0.001). There was no correlation between the rate of energy expenditure and the duration or degree of severity of the disease, and particularly the occurrence and magnitude of weight loss, which is frequently observed during the course of the disease. The relative energy expenditure was not significantly different between untreated and treated parkinsonian patients (18.8 +/- 3 p. 100 and 24.5 +/- 6.2 p. 100 respectively). Further investigations were designed to determine whether the increased energy expenditure could reflect a functional impairment of the automatic nervous system. The integrity of the vagus nerve was tested by plotting vs time the plasma Pancreatic Polypeptide levels in response to insulin-induced hypoglycaemia. A physiological stimulation was obtained in the 8 parkinsonian patients studied. This is not the case in chronic autonomic failure. On the contrary, the relative energy expenditure was significantly decreased in the 6 patients that were given a beta-blocking drug, pindolol, 15 mg daily for 3 weeks (+30.7 +/- 4.3 p. 100 before and +21 +/- 4.2 p. 100 after treatment; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Increase of energy expenditure in Parkinson's disease]. 201 81

Clinical studies suggest that gut disorders are common in Parkinson's disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinson's disease. We compared colonic tissue from 11 patients with advanced Parkinson's disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9.5. Nine of the 11 Parkinson's disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0.4 [SE 0.2] vs 6.9 [2.3] in controls and 5.7 [2.0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinson's disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinson's disease patients than in four controls (7.3 [5.1] vs 24.2 [4.6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinson's disease may lead to better treatment of colorectal dysfunction in this disease.
 ...
PMID:Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation. 756 69

Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the differentiation of neuronal cells, rescue them from naturally occurring death, and trigger neuronal regeneration. The NTFs bind to two classes of cell surface receptors, whereas CNTF receptor is composed of three subunits. The functions of these polypeptide survival factors with trophic action on nerve cells have recently been approached by the targeted disruption of the CNTF, NTF and their receptor genes by the homologous recombination technique. The embryonic growth and morphogenesis of these gene 'knock-out' mice is normal, but they develop with defects in various subsets of the peripheral nervous system, and the homozygous mutant mice often die during the early postnatal period. Disturbances in the biology of NTFs and CNTF have recently been implicated in the pathogenesis of certain common neurodegenerative disorders, such as Parkinson's disease, motor neurone diseases, and Alzheimer's disease. Intensive research on their pharmaceutical perspective has, therefore, been provoked. All neurotrophins and CNTF can now be synthesized on a large scale as biologically active recombinant proteins, and several alternatives for their local applications to the target tissue have been presented. Their therapeutic potential is discussed.
 ...
PMID:Neurotrophins and ciliary neurotrophic factor: their biology and pathology. 782 97

A susceptibility gene for Parkinson's disease (PD) with late onset and typical Lewy-body pathology maps to chromosome 2p13 (PARK3). In the present study we examined the gene for transforming growth factor alpha (TGF alpha), which is located in the PARK3-region, as a potential candidate gene. This polypeptide mitogen exerts trophic actions on dopaminergic neurons and TGF alpha-deficient mice have fewer dopaminergic neurons. We did not find mutations in the exonic or exon-flanking intronic sequences of index patients of two families linked to 2p13. This result excludes mutations in the coding region of TGF alpha as a cause for hereditary PD, but does not rule out a possible role of sequence variants in regulatory regions or splice sites.
 ...
PMID:Autosomal-dominant Parkinson's disease linked to 2p13 is not caused by mutations in transforming growth factor alpha (TGF alpha) (short communication). 1171 38

Intracellular filamentous aggregates comprised of alpha-synuclein such as Lewy bodies and glial cytoplasmic inclusions are the defining hallmarks of a subset of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. We have analyzed biochemical and structural properties of alpha-synuclein filaments assembled in vitro or extracted from brains of patients with multiple system atrophy and found that both types of filaments are insoluble to detergents and partially resistant to proteinase K digestion. Immunoelectron microscopy and immunoblot analysis showed that both amino and carboxyl termini of alpha-synuclein in in vitro assembled filaments were degraded by proteinase K treatment, whereas the central portion of alpha-synuclein is resistant to proteinase K and retains filamentous structures. Protein sequencing and mass spectrometric analyses of the proteinase K-resistant, minimal fragment of 7 kDa revealed that amino acid residues 31-109 of alpha-synuclein constitute the core unit of the filaments. These observations suggest that the central half of the alpha-synuclein polypeptide, containing five tandem repeats as well as a part of the carboxyl-terminal acidic region, forms the core structure of alpha-synuclein filaments, which is coated by the amino- and carboxyl-terminal portions at the periphery.
 ...
PMID:Biochemical characterization of the core structure of alpha-synuclein filaments. 1189 34

Protein aggregation and the formation of highly insoluble amyloid structures is associated with a range of debilitating human conditions, which include Alzheimer's disease, Parkinson's disease, and the Creutzfeldt-Jakob disease. Muscle acylphosphatase (AcP) has already provided significant insights into mutational changes that modulate amyloid formation. In the present paper, we have used this system to investigate the effects of mutations that modify the charge state of a protein without affecting significantly the hydrophobicity or secondary structural propensities of the polypeptide chain. A highly significant inverse correlation was found to exist between the rates of aggregation of the protein variants under denaturing conditions and their overall net charge. This result indicates that aggregation is generally favored by mutations that bring the net charge of the protein closer to neutrality. In light of this finding, we have analyzed natural mutations associated with familial forms of amyloid diseases that involve alteration of the net charge of the proteins or protein fragments associated with the diseases. Sixteen mutations have been identified for which the mechanism of action that causes the pathological condition is not yet known or fully understood. Remarkably, 14 of these 16 mutations cause the net charge of the corresponding peptide or protein that converts into amyloid deposits to be reduced. This result suggests that charge has been a key parameter in molecular evolution to ensure the avoidance of protein aggregation and identifies reduction of the net charge as an important determinant in at least some forms of protein deposition diseases.
 ...
PMID:Studies of the aggregation of mutant proteins in vitro provide insights into the genetics of amyloid diseases. 1237 55


1 2 3 4 5 6 7 8 9 10 Next >>