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)

In a series of 37 Parkinson's disease (PD) brains, cortical changes were reexamined by means of Bielschowsky silver impregnation and anti-ubiquitin immunocytochemistry. Compared to routine HE staining, anti-ubiquitin immunostaining revealed neocortical Lewy bodies (LBs) in a significantly higher percentage (76% vs. 32%). Neocortical senile plaques (SPs) occurred more frequently in brains with neocortical LBs than in cases without LBs (50% vs. 11%; p < 0.05). Semiquantitative assessment of neocortical LB density correlated with the frequency of occurrence and density of neocortical SPs. Dementia was confined to patients with abundant neocortical LBs, thus fulfilling histological criteria of diffuse Lewy body disease. We conclude that neocortical LBs are a very frequent feature of PD, although abundance of cortical LBs is confined only to a small subgroup with prominent dementia: diffuse Lewy body disease.
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PMID:Neocortical changes in Parkinson's disease, revisited. 820 26

Ubiquitinated cytoplasmic inclusions are a characteristic feature of the neuronal pathology of neurodegenerative diseases. Immunocytochemical techniques have identified intermediate filaments associated with ubiquitin-immunoreactive inclusions in Alzheimer's disease (AD), Parkinson's disease (PD), and Pick's disease; however, no core protein has been detected in the ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS). The pathogenesis of these inclusions is not known, but the inclusion may result from an accumulation of an abnormal proteins. Here we report a novel protein of 32.5 kDa detected by polyacrylamide gel electrophoresis, in the spinal cord in ALS patients. A polyclonal antibody raised against this protein and used for Western blotting, suggests that the novel protein is related to actin. Immunocytochemical studies using this antibody indicate that the protein is found in Lewy body-like inclusions in anterior horn cells of ALS, and in Lewy bodies in the substantia nigra in PD.
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PMID:Antibody to an abnormal protein in amyotrophic lateral sclerosis identifies Lewy body-like inclusions in ALS and Lewy bodies in Parkinson's disease. 824 23

We report a family with autosomal dominant parkinsonism. The propositus developed parkinsonism at a relatively young age (45 years) and came to autopsy after a 6-year illness. She had typical features of Parkinson's disease except for an absence of rest tremor, although this was present in other family members. A diagnosis of Lewy body parkinsonism was confirmed by neuropathological examination. Additional pathological features included the presence of cortical Lewy bodies and anti-ubiquitin-positive neurites in the cornu Ammonis 2 and 3 (CA2-3) region of the hippocampus. This kindred is similar both clinically and pathologically to a few previously reported pedigrees, further strengthening recent evidence of a genetic etiology of some forms of Parkinson's disease.
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PMID:Autosomal dominant Lewy body parkinsonism in a four-generation family. 828 94

Three cases of Lewy body disease were investigated in order to compare the morphological and immunohistochemical characteristics of the neuronal inclusions in the cerebral cortex (CC) and brain-stem (BS). Ultrastructurally, the CC contained intermediate-sized filaments with variable amounts of granular material and other organelles, whereas the BS consisted of an electron-dense core and an outer area with radially oriented filaments. The cerebral cortex was immuno-reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and differed from BS. In addition, although the CC were antigenically similar to BS in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the localization of neurofilament immunoreactivity differed between them, being confined positively to the core of CC, but to the periphery of the BS. Although Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to BS, they have been reported to differ in their immunoreactivity with antibodies against tau. It has been reported that CC differ from LB with regard to immunoreactivity with antibodies against TH and tropomyosin. It is inferred that these inclusions (CC, BS and LB) differ in morphogenesis.
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PMID:Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem in Lewy body disease. 829 42

We have shown that following heat shock (42.5 degree C for 30 min), mouse-derived C1300 N2A neuroblastoma cells contain increased levels of mRNA coding for the inducible form of heat shock protein 70 and for ubiquitin. Incubation of C1300 cells with iron also induces an elevation in content of mRNAs coding for the same two proteins that can be blocked by alpha-tocopherol and desferrioxamine. Iron was shown to increase mitochondrial and lysosomal activities in differentiated C1300 N2A cultures, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red cytotoxicity assays. These responses were not initially associated with any loss of viability, as assessed by the lactate dehydrogenase release assay. These results suggest that there is production of cytoprotective heat shock proteins in response to iron-mediated cell damage, probably involving free radical generation, in neural cells. The apparent stress response of vulnerable neurones in human neurodegenerative diseases, particularly Parkinson's disease, may be induced by iron-mediated free radical production in degenerating neurones, making investigation of the mechanism of free radical-induced responses in neuronal cells of special interest.
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PMID:Changes in heat shock protein 70 and ubiquitin mRNA levels in C1300 N2A mouse neuroblastoma cells following treatment with iron. 838 Apr 40

This chapter reports the clinical and neuropathological findings of eight cases of "diffuse Lewy body disease" verified by autopsy. The age at onset was between 60 and 82 years; the age at death was between 75 and 92 years. The initial symptoms were amnesia in three cases, orthostatic dizziness in three, visual hallucination in two, but parkinsonism in none. The cardinal clinical symptoms included dementia in all cases, hallucinatory-delusional state in six, akinesia and rigidity in five, and orthostatic hypotension in five. Antemortem diagnoses were senile dementia in five, and hallucinatory-delusional state, Parkinson's disease and Shy-Drager syndrome in one each. Despite the clinical symptoms differences from each other, neuropathological findings were alike. Abundant Lewy bodies were present in the neurons of the cerebral cortex as well as in the brainstem nuclei and diencephalon. Concomitant senile changes including senile plaques and Alzheimer's neurofibrillary tangles (NFTs) were also present in varying degree. Immunocytochemical study with anti-ubiquitin for Lewy body, anti-tau protein for NFT, and beta-protein of amyloid for senile plaque suggested that dementia of DLBD might have resulted not from a single pathology but from the complex of Lewy bodies, NFTs and senile plaques.
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PMID:Clinical and neuropathological aspects of diffuse Lewy body disease in the elderly. 842 Jan 71

The Chamorro population of the island of Guam is highly susceptible to a disease called lytico-bodig (LB), which clinically resembles a mixture of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer disease (AD). The disease is characterized by the widespread development of neurofibrillary tangles in the central nervous system. These tangles have an immunohistochemical profile indistinguishable from that seen in AD. We studied by immunohistochemistry the occurrence of intracellular and extracellular neurofibrillary tangles in LB in the entorhinal cortex, hippocampus and substantia nigra using antibodies to tau protein and ubiquitin. We also studied the relationship of these tangles to amyloid precursor protein (APP) and its beta-amyloid fragment (BAP), using multiple antibodies to BAP and other APP sequences. In advanced cases of LB, the development of neurofibrillary tangles was far more severe than in advanced cases of AD. Virtually all neurons of CA-1 and the subiculum were lost and only ghost tangles remained. In areas dominated by such extracellular tangles, BAP deposits were frequently observed developing around the fibers of ghost tangles. In some cases, the deposits covered only a few of the fibers, but in others, they seemed to envelope the complete tangle. The deposits were thioflavin S and Congo red positive, indicating that the BAP was in a consolidated form. We describe these entities as "tangle-associated amyloid deposits". Such BAP deposits have previously been described in some cases of AD, dementia pugilistica and LB. However, we found them in all cases of LB with dementia in the hippocampal-entorhinal areas and in most cases in the substantia nigra. They do not evolve from diffuse BAP deposits since they are remote from them, and they do not trap dystrophic neurites. The fact that extracellular tangle material can act as a nidus for BAP build-up in LB suggests that further consideration needs to be given to the ways in which extracellular BAP deposits are formed.
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PMID:Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in Guamanian parkinsonism-dementia. 852 3

Patients with the Lewy body variant (LBV) of Alzheimer's disease (AD) meet diagnostic criteria for AD but have a lighter burden of plaque and tangle AD pathology despite comparable dementia. We quantified neocortical Lewy bodies (LB) in LBV patients (n = 14) using anti-ubiquitin polyclonal antibody, selecting for quantification those neocortical regions with the highest densities of LB. Neocortical neurofibrillary tangles (NFT) and neuritic plaques were evaluated with thioflavin- S. A group of classical AD patients (n = 12), matched for disease duration, was also studied. For most of these cases, entorhinal neurofibrillary pathology had previously been assessed by applying a modification of the Braak and Braak AD staging protocol. Although LBV and AD groups had similar mental test scores when last evaluated prior to death, lower neocortical NFT and plaque counts and lower modified Braak stages were observed in LBV. Neocortical NFT counts correlated with impaired neuropsychological test performance in AD but not in LBV. Plaque counts did not correlate with mental status in either group. Lewy body concentrations in four neocortical areas correlated significantly with dementia severity in LBV. The association of AD lesions in the neocortex with dementia in LBV was comparatively weaker than that observed for LB concentrations. These findings suggest that neocortical LB combined with entorhinal NFT or subcortical Parkinson's disease-type pathology may equalize the degree of dementia seen in LBV with that encountered in classical AD.
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PMID:Neocortical lewy body counts correlate with dementia in the Lewy body variant of Alzheimer's disease. 855 71

Characteristic ubiquitin-positive, tau-negative, degenerating neurites were present in brainstem regions known to be involved in idiopathic Parkinson's disease. Corresponding changes were entirely absent from controls and from the brainstems obtained from patients who had died with Alzheimer's disease, motor neuron disease and multiple system atrophy. In Parkinson's disease cases degenerating neurites were particularly striking in the dorsal motor nucleus of the vagus. In this nucleus the density of degenerating neurites was inversely related to the duration of Parkinson's disease symptoms. Some ubiquitin-positive degenerating neurites also contained neurofilament immunoreactivity. However, confocal microscopy revealed that ubiquitin and neurofilament reactivities were located in separate regions of the degenerating neurite, suggesting that proteins other than neurofilaments may be important in the process of ubiquitination. The demonstration of ubiquitin-positive degenerating neurites in routinely prepared paraffin-embedded material, particularly in the dorsal motor nucleus of the vagus, could become diagnostically useful in those Parkinson's disease cases in which Lewy bodies are difficult to find. Demonstration of extensive ubiquitin-positive degenerating neurites might provide a clue to disease activity at the time of death.
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PMID:Ubiquitin-positive degenerating neurites in the brainstem in Parkinson's disease. 859 76

Lewy bodies (LBs) are the pathological hallmarks of degenerating neurons in the brains of patients with Parkinson's disease and diffuse Lewy body disease. We developed a novel purification procedure for LBs using sucrose density separation followed by fluorescence-activated particle sorting, and we raised > 15 monoclonal antibodies to LBs purified from diffuse Lewy body disease brains. The monoclonal antibody that stained the largest number of LBs most intensely did not recognize ubiquitin in free or monoubiquitinated forms nor the ubiquitin conjugating enzymes, but it did react with polyubiquitin chains as well as with high molecular weight polyubiquitinated LB-derived proteins. Thus, these results suggest that LBs contain polyubiquitin chains. Although polyubiquitination of LB proteins may trigger ubiquitin-proteasome proteolytic pathways, the incomplete activation of these pathways could play a mechanistic role in the formation of LBs in neurodegenerative diseases.
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PMID:Purification and characterization of Lewy bodies from the brains of patients with diffuse Lewy body disease. 862 21


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