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 nature of Lewy bodies (LBs) in the brain stem and cerebral cortex in five cases of diffuse Lewy body disease and one case of Parkinson's disease with dementia were investigated immunocytochemically with various antibodies to cytoskeletal proteins, paired helical filaments (PHF) and ubiquitin. Antibodies to 200-kDa component of neurofilament, tau and PHF showed no significant reactions with most of LBs. Antibodies to high-molecular weight microtubule-associated proteins (HMWMAPs) moderately stained the periphery of a few of LBs. A monoclonal antibody to PHF (DF2) which recognizes ubiquitin, and polyclonal antibodies to ubiquitin immunostained virtually all of the typical and cortical LBs as intensely as Alzheimer's neurofibrillary tangles and senile plaque neurites: the periphery of LBs was darkly stained, whereas the central core of typical LBs and central zone of cortical LBs were less intensely stained or remained unstained. Immunoelectron microscopy of the LBs with DF2 revealed that immune reaction products were located on the filaments exclusively in the periphery of LBs, but not on those in the center. These findings suggest that both types of LBs are immunocytochemically indistinguishable despite some structural differences, and that peripherally located filaments in LBs are tagged with ubiquitin, an element required for the ATP-dependent proteolysis system in the cell. Antibodies to ubiquitin are the most useful marker of LBs ever known.
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PMID:Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. 336 59

The immunoreactivity of cortical and brainstem-type Lewy bodies has been investigates with antibodies to the cyclin-dependent kinase 5 (cdk5), to the extracellular regulated kinase 1 (ERK-1), and to the cdc2p34 kinase and with antibodies specific for phosphorylation epitopes typical of paired helical filament-tau (PHF-tau). Both cortical and brainstem-type Lewy bodies in diffuse Lewy body disease and brainstem-type Lewy bodies in Parkinson's disease were found to be immunoreactive for cdk5 but not for cdc2p34 or ERK-1 or with the PHF-tau antibodies. Double immunolabeling showed that cdk5-positive Lewy bodies were also ubiquitin immunoreactive and that cdk5 antibodies labeled as many Lewy bodies as ubiquitin antibodies in adequately fixed tissue. The cdk5 immunoreactivity of Lewy bodies was abolished by preabsorption of the antibody with a cdk5 peptide. The antibodies to cdk5 labeled a single 33-kd species on Western blots of human brain homogenates, with a similar intensity in control, diffuse Lewy body disease, and Alzheimer's disease, and this cdk5 species was found mainly in the particulate fraction of brain homogenates. This observation suggests that cdk5 might be a protein kinase involved in the phosphorylation of a molecular component of Lewy bodies, for example, neurofilament proteins known to be present in these inclusions.
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PMID:Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. 748 9

The frequency of the apolipoprotein E (ApoE) epsilon 4 allele and its relationship with coexistent Parkinson's disease (PD) neuropathology in Alzheimer's disease (AD) have not been extensively explored. We determined ApoE genotype in 100 dementia patients with neuropathologically confirmed AD with and without concomitant Parkinson's disease (PD) changes (nigral degeneration and Lewy bodies at various sites). Fifty "AD+PD" patients were matched closely with 50 "pure AD" patients for age, sex, and duration of dementia. We found identical overrepresentation of the epsilon 4 allele in the two groups: 72% of the patients in each group had at least one ApoE epsilon 4 allele, compared with approximately 25% in the general population (p < 0.005) and in our institutional autopsy population (p < 0.001). Age at onset varied inversely with epsilon 4 allele dosage in men but not in women in both the AD and the AD+PD groups. As with amyloid deposition and plaque frequency in AD, we observed an association between epsilon 4 dosage and PD-related changes. Specifically, the severity of ubiquitin-positive neuritic change in CA2/3 of the hippocampus, but not the frequency of cortical Lewy bodies, varied significantly with epsilon 4 dosage in the AD+PD cases.
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PMID:Alzheimer's disease with and without coexisting Parkinson's disease changes: apolipoprotein E genotype and neuropathologic correlates. 750 Nov 46

Impaired olfaction occurs in patients with idiopathic Parkinson's disease (PD), and Lewy bodies have been found in the olfactory bulb and tract. We now confirm the latter finding and show that this presence of Lewy bodies is associated with significant neuronal loss. A quantitative study of the anterior olfactory nucleus (AON) was performed in tissue obtained postmortem from seven patients with PD and seven age-matched controls. Neuronal loss was seen in the PD bulb and tracts (p < 0.01), and a strong correlation of neuronal loss with disease duration was detected (R = -0.87). The presence of Lewy bodies was confirmed with immunocytochemical staining for ubiquitin in all the PD cases.
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PMID:The anterior olfactory nucleus in Parkinson's disease. 765 44

We investigated CA2/3 ubiquitin-immunoreactive neurites in 120 cases of diverse neurodegenerative diseases. This neuritic change occurred in 25 of 30 cases of Alzheimer's disease (AD) with coexistent Parkinson's disease (PD) changes, as well as two cases of PD and two cases of progressive supranuclear palsy. All 29 cases with neuritic change showed cortical Lewy bodies. Neuritic change was absent in 86 cases of neurodegenerative diseases without Lewy bodies, including 66 cases of pure AD. Thus, ubiquitin-immunoreactive CA2/3 neurites and cortical Lewy bodies, frequently coexist; this association appears to be independent of the presence or absence of coexistent pathologies, eg, AD. Moreover, in and of itself, nigral degeneration without Lewy bodies, such as that encountered in other (non-PD) movement disorders, apparently is not associated with CA2/3 neuritic change.
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PMID:Ubiquitin-positive CA2/3 neurites in hippocampus coexist with cortical Lewy bodies. 767 45

A 71-year-old man developed signs of progressive dementia, followed by extrapyramidal and motor neuron disease symptoms, which led to death in 6 years. Neuropathological examination revealed neuritic plaques, neurofibrillary tangles, and Lewy bodies in the substantia nigra and neocortex. Atrophy and gliosis with intraneuronal ubiquitin inclusions were present in the anterior horns of the spinal cord. Overlapping of Alzheimer's disease, Parkinson's disease, diffuse Lewy body disease and amyotrophic lateral sclerosis is rare and can increase our understanding of the process of neurodegeneration.
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PMID:Concurrence of Alzheimer's disease, Parkinson's disease, diffuse Lewy body disease, and amyotrophic lateral sclerosis. 773 98

Forty-eight cases of pathologically verified Alzheimer's disease were examined for the presence of ubiquitin-positive cortical Lewy bodies (CLBs). Thirty-four (71%) of 48 cases of Alzheimer's disease had CLBs compared with 4 (44%) of nine patients with idiopathic Parkinson's disease, and 2 (20%) of 10 patients with multi-infarct dementia. None of the 18 cognitively intact elderly controls we examined had CLBs. Among Alzheimer's disease patients, there was a strong correlation between CLBs and degenerative changes in the substantia nigra. We also found an association between the presence of CLBs and extrapyramidal symptoms. Among Alzheimer's disease patients, there was no association of CLBs with either senile plaques or neurons containing neurofibrillary tangles in hippocampus, neocortex, or ventral striatum. The incidence of CLBs among pathologically verified Alzheimer's disease cases is high when a careful search for these inclusions is performed with a sensitive method such as anti-ubiquitin immunocytochemistry.
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PMID:Cortical Lewy bodies in Alzheimer's disease. 774 74

One of the characteristic histological features of Parkinson's disease (PD), with or without dementia, is the presence of Lewy bodies (LBs) in the brainstem and neocortical and limbic structures. They are often accompanied by Alzheimer type pathology (ATP). In the present retrospective study the clinical features and post-mortem findings of 18 consecutive and unselected PD patients were compared, with special reference to the frequent but not exclusive association of LBs with ATP in Lewy body disease (LBD). LBD is the term applied to a particular pattern of neuronal degeneration associated with LBs. In this study of idiopathic PD patients ATP seems to be the major determinant of the cognitive decline in most patients. Cortical Lewy Bodies (CLBs) were present in all patients reviewed, whether or not dementia was present. It was not possible to distinguish a specific pattern in the cognitive or psychopathological symptoms of dementia that would differentiate LBD from Alzheimer's disease (AD). Although in most cases hippocampal CA2-3 ubiquitin immunoreactive neurites were observed, here again there was no correlation with the presence of dementia.
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PMID:'Lewy body disease': clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia. 778 67

Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocytochemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.
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PMID:Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. 791 27

The ATP-ubiquitin-dependent proteolytic pathway (ubiquitin pathway) is believed to be involved in the formation of various neuronal inclusion bodies including Lewy bodies (LBs), a pathological hallmark of Parkinson disease and diffuse Lewy body disease (DLBD). Since multicatalytic proteinase (MCP) is involved in the ubiquitin pathway, an investigation of whether MCP is involved in neuronal inclusion bodies would provide a clue to the mechanism underlying the formation of neuronal inclusion bodies as well as to the pathogenesis of degenerative neurological disorders. In this study, we investigated detailed immunolocalization of MCP in LBs in DLBD brains using light and electron microscopy. We raised three different monoclonal antibodies against purified human MCP. Each of them recognized different sets of MCP subunits on Western blotting. Immunohistochemically, anti-MCP antibodies recognized all ubiquitin-positive cortical LBs in situ as well as those isolated from frozen DLBD cortices, suggesting that MCP is present in LBs as a whole molecule exhibiting protease activity. In electron microscopy, MCP immunoreactivity (MCP-IR) was exclusively localized on a characteristic oval structure with an approximate diameter of 100 nm. This structure was distributed throughout the LBs and was devoid of ubiquitin immunoreactivity. Treatment of isolated LBs with 2% SDS, but not with 0.5% Triton X-100, removed this structure from LBs in which fibrous materials predominated. Ubiquitin immunoreactivity was also decreased in isolated LBs treated with 2% SDS, suggesting that the fibrous structures in LBs were not ubiquitinated in situ. Thus, it is suggested that LBs are subjected to a proteolytic process in which MCP plays a role via processing of specific components of LBs.
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PMID:Multicatalytic proteinase is associated with characteristic oval structures in cortical Lewy bodies: an immunocytochemical study with light and electron microscopy. 802 94


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