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 Lewy body is an intraneuronal inclusion body that is one of the histologic hallmarks of Parkinson's disease, a degenerative disease of the brain. Ultrastructural analysis has shown that the Lewy body is composed of straight 7-20 nm filaments and amorphous elements. Previous light microscopic, immunocytochemical studies have suggested the presence of neurofilament, microtubule, ubiquitin, and paired helical filament-related epitopes in Lewy bodies. Yet the biochemical composition of the Lewy body remains incompletely elucidated. The ultrastructural and immunocytochemical similarities and differences between the Lewy body and the neurofibrillary tangle of Alzheimer's disease raise questions as to their relation to each other and possible shared mechanisms of formation. In this study the authors examine whether ultrastructural immunocytochemical analysis of Lewy bodies confirms the light microscopic data, whether the structures and epitopes of Lewy bodies share with Alzheimer's disease neurofibrillary tangles the property of insolubility in sodium dodecyl sulfate, and speculate about the subunit composition of Lewy body filaments.
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PMID:Filaments of Lewy bodies contain insoluble cytoskeletal elements. 131 25

The etiology of nerve cell death in neuronal degenerative disease is unknown, but it has been hypothesized that excitotoxic mechanisms may play a role. Such mechanisms may play a role in diseases such as Huntington's disease, Parkinson's disease, amyotropic lateral sclerosis, and Alzheimer's disease. In these illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden release of glutamate, such as occurs in ischemia. One possibility, however, is that a defect in mitochondrial energy metabolism could secondarily lead to slow excitotoxic neuronal death, by making neurons more vulnerable to endogenous glutamate. With reduced oxidative metabolism and partial cell membrane depolarization, voltage-dependent N-methyl-D-aspartate (NMDA) receptor ion channels would be more easily activated. In addition, several other processes involved in buffering intracellular calcium may be impaired. Recent studies in experimental animals showed that mitochondrial toxins can result in a pattern of neuronal degeneration closely resembling that seen in Huntington's disease, which can be blocked with NMDA antagonists. NMDA antagonists also block neuronal degeneration induced by 1-methyl-4-phenylpyridium, which has been implicated in experimental models of Parkinson's disease. The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging. If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects.
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PMID:Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? 134 66

Parkinson's disease (PD) is a common degenerative disease, but its etiology is still unknown. However, since the discovery of MPTP, many investigators have been interested in the mitochondrial function in PD. We investigated mitochondrial functions in PD patients using the methods which have successfully been applied to mitochondrial myopathies (MM), i.e. assay of lactate and pyruvate, measurement of muscle mitochondrial respiratory enzyme activities and Southern blot analysis of muscle mitochondrial DNA. Parkinson's disease patients did not differ from controls in the mean blood and CSF (cerebrospinal fluid) lactate and pyruvate levels at the basal resting state or during an aerobic exercise. But mitochondrial complex I activity of the skeletal muscle was significantly decreased in PD. In the Southern blot analysis, we could not find major deletions or insertions of mitochondrial DNA in PD. Our studies disclosed a differential mitochondrial impairment between PD and MM. We discuss the implication of our observation.
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PMID:Is Parkinson's disease a mitochondrial disorder? 157 31

The term neurodegenerative denotes a process rather than a state. In contrast, most research on such disorders, whether clinical or experimental, represents only a slice of time. Their progressive nature is mostly confined to speculation instead of being codified in research protocols. Research on cancer, also a degenerative disease, is much more often framed in terms of process. Part of the difference is accounted for by the impact of quantitative modeling, which enjoys a long history in both basic and clinical cancer research and which originated in attempts to describe and understand tumor development. Analogous questions are posed by neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Among the issues that modeling could help to clarify are the properties and sources of the age-specific incidence rate, which resembles that for cancer, and the pharmacokinetics governing the toxic products of neurotransmitter metabolism. Neurodegenerative disorders maintain a research advantage because functional measures, mostly inaccessible to cancer investigators, serve as the ultimate index of progression. Their exploitation, however, in longitudinal studies remains inadequate.
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PMID:Cancer and the dynamics of neurodegenerative processes. 174 29

We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.
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PMID:Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients. 235 20

The molecular pathology of chronic degenerative disease is not understood. Generally there must be two related, but opposing, processes: the direct deleterious effects of the pathogenic insult which can be chemical or viral and a cellular cytoprotective response to the insult. We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in some major chronic degenerative diseases: the inclusions contain ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease and alcoholic liver disease as well as astrocytomas and a myopathy. Protein ubiquitination is considered a signal for extra-lysosomal protein degradation although ubiquitin-protein conjugation may have several other important functions. Intermediate filaments are a component of some of the inclusions in diseased cells; we have previously reported that they are involved in protein sequestration for degradation by lysosomally mediated autophagy. Therefore, intermediate-filament-containing ubiquitinated inclusions may be hallmarks of cellular attempts to eliminate pathogenic insults by activating protein degradation mechanisms. Ubiquitinated inclusions could also be a hallmark of viral infections: they are in polio-virus-infected anterior horn neurones and Epstein-Barr-transformed lymphoblastoid cells. Some of the clinical observations can be reproduced experimentally in tissue culture cells. The implications of the combined clinical and experimental observations for cell sanitization and protein catabolism will be discussed.
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PMID:Intermediate filament-ubiquitin diseases: implications for cell sanitization. 255 34

The selective monoamine oxidase (MAO) type B inhibitor has proven to be a useful adjunct to L-dopa therapy of Parkinson's disease. Although not all features of its anti-Parkinson action is known, studies on brains obtained at autopsy from patients on (-)deprenyl show that the selective inhibition of MAO B with a concomitant increase of dopamine, but not of serotonin, in the basal ganglia may be responsible for its mode of action. The increased life expectancy noted in Parkinsonian patients on long term (-)deprenyl therapy (9 years) is another unexpected feature of the drug (Birkmayer et al., 1985). This exciting data, if confirmed in other long term clinical trials, may herald a new approach for the treatment of this degenerative disease, since more recent studies indicate that Parkinson's disease may eventually turn out to be a neurotoxic event (see Snyder and D'Amato, 1986, for review). Thus selective MAO type B inhibitors could represent a unique class of drug, having both therapeutic and preventive actions in one.
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PMID:Pharmacology of MAO B inhibitors: mode of action of (-)deprenyl in Parkinson's disease. 309 63

The locus ceruleus was studied in 86 brains of the elderly, with or without degenerative disease. Parkinson's disease, multiple system atrophy, progressive supranuclear palsy and senile dementia were among the diseases studied. Nerve cell loss, the appearance of neurofibrillary changes and Lewy bodies were examined semi-quantitatively. The number of nerve cells diminished in old age, especially over 90 years. The decrease of nerve cells was greater in cases with Lewy bodies. A marked loss of nerve cell was observed in multiple system atrophies, including Shy-Drager syndrome, olivopontocerebellar atrophy and striatonigral degeneration, and in some cases of Parkinson's disease and senile dementia. The number of nerve cells did not decrease in cases of progressive supranuclear palsy. Lewy bodies and neurofibrillary tangles appeared increasingly in old age. However, the incidence of both changes in the same neuron was rare, and in such cases their structures appeared not to be related.
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PMID:Neuropathology of the locus ceruleus: a semi-quantitative study. 619 83

Parkinson's disease, a classic human degenerative disease, is one of the commonest neurological disorders. Although this movement disorder had been defined a century and a half ago, its aetiology remains unknown. Some environmental factors are suspected to play a key role in induction of slow progressive loss of nigral dopaminergic neurons. Nerve cell death seems to be produced via cytotoxic oxygen radicals which are accumulated in the pars compacta of the substantia nigra. The major biochemical abnormality in parkinsonism is a decrease in the dopamine synthesis although other neurotransmitters are affected too. Several animal models of Parkinson's disease have been introduced to study mechanisms of selective degeneration of the substantia nigra and to assess effectiveness of various therapeutic approaches. Present pharmacological treatment, directed toward replacement of missing dopamine, uses high-dosage of levodopa. However, this therapy helps the symptoms but do not halt the disease. Doses of levodopa have to be increased as symptoms increase in severity, which is associated with severe side effects. Neural transplantation of catecholamine-producing cells seems to be a new promising tool for treatment of Parkinson's disease. Grafts of adrenal medulla, carotid body, pheochromocytoma, sympathetic ganglion and embryonic dopaminergic cells, either in a form of solid pieces or cell suspension, were inoculated into the experimentally denervated striatum of rats and subhuman primates. At present, more than 300 parkinsonian patients have received autologous adrenal medulla or human embryonic nigral grafts but results are still controversial. Attempts for transplantation treatment retreated to the laboratories and researchers are currently seeking to select the best king of cells capable of producing dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parkinson's disease: contemporary state and perspectives. 776 92

The recent molecular cloning of BDNF and CNTF based on traditional protein purification and protein sequencing and the identification and cloning of NT-3 and NT-4 by homology cloning strategies has led to a tremendous flurry of interest in the biology of these proteins and initiation of studies to assess their potential utility in neurological disorders ranging through degenerative disease, stroke and ischemia, trauma and peripheral neuropathies. Tissue culture studies have been very useful in identifying neuronal specificities of the neurotrophins and CNTF and in combination with localization studies of these growth factors and their receptors have provided the basis for in vivo studies. Initial animal studies with BDNF indicate efficacy of BDNF in models of Alzheimer's and Parkinson's disease and small fiber sensory neuropathy. Studies with CNTF have similarly progressed from in vitro findings, especially the discovery that CNTF is a growth factor for motor neurons, to in vivo findings where CNTF has been shown to be effective in slowing symptoms of motor neuron dysfunction in three genetic models. Based on these positive animal data, CNTF is currently in clinical trials for the potential treatment of motor neuron disease or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
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PMID:Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor. 783 3


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