Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the expression of ubiquitin in anterior horn cells of various subgroups of adult-onset motor neuron diseases (MNDs). Ubiquitin-positive skein-like inclusions (SLIs) were found in all 11 cases of sporadic amyotrophic lateral sclerosis (ALS) patients, two patients with lower MND, 3 sporadic cases of ALS with dementia, 3 sporadic ALS cases with long-term use of respirators, and two cases of sporadic ALS with Lewy body-like hyaline inclusions. This result suggests that a similar pathomechanism is involved in the degeneration of the lower motor neurons in these subgroups. SLIs were not detected in two cases of adult-onset MND with basophilic inclusions. This may indicate that adult-onset MND with basophilic inclusions is a distinct nosological entity of classical ALS and some relationship to juvenile ALS with basophilic inclusions is suggested.
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PMID:[A comparative immunohistochemical study of ubiquitin-positive skein-like inclusions in anterior horn neurons in subgroups of adult-onset motor neuron diseases]. 812 68

Ubiquitin is a stress protein implicated in the degradation of short-lived and abnormal proteins. In a neuropathological study of 43 cases with motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and 44 control cases the distribution and specificity of Bunina bodies and ubiquitin-reactive inclusions (UBRI) were investigated. The primary motor area showed nerve cell loss in 67%, Bunina bodies in Betz cells (10%) and UBRI in small pyramidal cells (17%). Degeneration of anterior horn cells in all cases coincided with Bunina bodies (84%) and UBRI (98%) in the same location; the motor nuclei of the caudal brain stem were also involved almost to the same degree. More resistant nuclei like the oculomotor nuclei or the Onuf's nucleus showed no degeneration but UBRI in 11% and 18% of cases, respectively. Like the degenerative process, the formation of UBRI was not confined to motor nuclei but also involved the brain stem reticular formation, substantia nigra, and Clarke's nucleus showing that MND/ALS is a multiple system degeneration. UBRI were found in only one control case in the anterior horn cells and in one case in the hypoglossal nucleus showing that UBRI, although not being absolutely specific for MND/ALS, have practical value for the neuropathological diagnosis of that disease. The pathogenetical implications of UBRI in MND/ALS are discussed.
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PMID:Motor neuron disease/amyotrophic lateral sclerosis--lessons from ubiquitin. 830 13

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.
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PMID:Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: a comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and Werdnig-Hoffmann disease. 838

Ubiquitin has been shown by immunohistochemical studies to be a component of many of the filamentous inclusion bodies that are known in neuropathology. In the current study, we examined the expression of ubiquitin in 14 cases of typical inclusion body myositis, in skeletal muscle specimens from four cases of typical amyotrophic lateral sclerosis, and in muscle specimens from three normal controls. In the cases of inclusion body myositis, rimmed vacuoles were ubiquitin immunoreactive in all cases. Intrasarcoplasmic inclusions were positive in the nine cases that had them. In four cases, there were positive intranuclear inclusions, and in seven, there was homogeneous staining of nuclei. Atrophic fibers and necrotic fibers were positive in 11 and nine cases, respectively. In the cases of amyotrophic lateral sclerosis, atrophic fibers were positive in three cases, and focal nuclear staining was seen in two. In one of the three control cases, a few atrophic fibers had faint sarcoplasmic positivity; no other staining was seen. We conclude that ubiquitin is a component of the inclusions that characterize inclusion body myositis. However, ubiquitin expression in skeletal muscle disease is not pathognomonic of inclusion body myositis.
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PMID:Ubiquitin expression in inclusion body myositis. An immunohistochemical study. 839 51

This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American "C" family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule-associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single-site GCC to GTC substitution at codon 4 (Ala4 --> Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with Ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.
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PMID:Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement. 878 8

This report concerns a case of sporadic amyotrophic lateral sclerosis (ALS) with dementia and Lewy body-like hyaline inclusions (LBHIs). The patient was a 70-year-old woman who initially showed memory disturbance and later developed bulbar palsy, muscle atrophy and weakness. The total clinical course was 51 months. The postmortem examination revealed superficial sponginess and subcortical gliosis in the frontotemporal cortices. Ubiquitin-positive intraneuronal inclusions were found in small cortical neurons of the frontotemporal lobe. Neuronal loss was marked in the spinal anterior horn with degeneration of the pyramidal tracts. The anterior horn cells had ubiquitin-immunoreactive skein-like inclusions and Bunina bodies. LBHIs were present in the lumbar horn; ultrastructurally they were composed of randomly arranged thick filamentous structures studded with granules. The LBHIs were intensely stained with anti-ubiquitin antibody. As in familial ALS and in certain cases of sporadic ALS, some of these inclusions reacted with an antibody against Cu/Zn superoxide dismutase, the enzyme whose gene was recently found to be mutated in some forms of familial ALS.
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PMID:Sporadic amyotrophic lateral sclerosis with dementia and Cu/Zn superoxide dismutase-positive Lewy body-like inclusions. 899 56

Ubiquitin-immunoreactive neuronal inclusions in the granular cells in the dentate fascia (UNIDs) of patients with multiple system atrophy (MSA) were examined for immunohistochemical and ultrastructural characterization especially in comparison with those which were recently reported for amyotrophic lateral sclerosis with dementia (ALS-D). Eight of 23 MSA patients had UNIDs which were also identified by Gallyas-Braak impregnation but immunonegative for other antibodies including against tau, neurofilaments, and alphaB crystallin. Ultrastructurally, loosely aggregated fibrils without limiting membrane located around the nucleus, which was confirmed by the results of ubiquitin-immunoelectron microscopy. The formation of UNIDs in MSA and ALS-D was suggested to be caused by different types of degeneration because UNIDs in MSA differ from these in ALS-D in terms of their stainability by Gallyas-Braak impregnation and ultrastructurally. In this study hippocampal involvement in MSA differing from ALS-D was clarified.
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PMID:Neuronal inclusions in the dentate fascia in patients with multiple system atrophy. 918 74

In a previous report we suggested that muscle fibers in distal myopathy with rimmed vacuoles (DMRV) were degraded by both lysosomal proteolysis (cathepsins) and Ca2+-dependent, nonlysosomal proteolysis (calpain). Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, we examined the role of the ATP-ubiquitin-dependent proteolytic pathway (proteasomes) in myofiber degradation in this myopathy. Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak. Quantitative analysis showed more reactivity for proteasomes in DMRV muscles and, to a lesser extent, in muscles from muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis patients. In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers. Ubiquitin accumulation was marked within rimmed vacuoles and was seen less extensively in the cytoplasm of atrophic fibers. The latter proteins colocalized well. In other diseased muscles, proteasomes and ubiquitin showed a positive reaction in the atrophic or necrotic fibers. The results indicate increased proteasome and ubiquitin in these muscle fibers as well as in other diseased muscle fibers. We suggest that the ATP-ubiquitin-proteasome proteolytic pathway as well as the nonlysosomal calpain and the lysosomal proteolytic pathway may participate in the muscle fiber degradation in DMRV.
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PMID:Proteasomes in distal myopathy with rimmed vacuoles. 980 76

Proton magnetic resonance spectroscopy (1H-MRS) was used to measure the in vivo signal of N-acetylaspartate (NAA), a putative neuronal marker, in the brain of the mutant wobbler mouse, a model of motor neuron disease. The ratio of NAA to creatine-phosphocreatine, an internal standard, was significantly lower in five affected wobbler mice (0.79+/-0.05; mean+/-s.d.) than in five unaffected littermates (0.98+/-0.10, p = 0.006). Ubiquitin and phosphorylated heavy neurofilament immunoreactivities were increased in cortical neurons of affected animals. This is the first demonstration of cerebral neuronal pathology in the wobbler mouse, supporting its use as a model of amyotrophic lateral sclerosis. In vivo IH-MRS and correlative postmortem study of wobbler mouse brain will allow temporal monitoring of neuronal degeneration and responsiveness to neuroprotective pharmacotherapies.
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PMID:Neuronal pathology in the wobbler mouse brain revealed by in vivo proton magnetic resonance spectroscopy and immunocytochemistry. 980 13

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia.
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PMID:Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy. 1065 Oct 32


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