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)

Ubiquitin-positive intraneuronal inclusions were found in the extramotor cortices of ten presenile dementia patients with motor neuron disease. There were inclusions in the hippocampal granular cells and in the small neurons of the superficial layers of the temporal and frontal cortices. Bunina bodies were present in the anterior horn cells in all cases. These results suggest that ubiquitin-related cytoskeletal abnormalities are common in cerebral non-motor small neurons in these patients.
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PMID:Ubiquitin-positive intraneuronal inclusions in the extramotor cortices of presenile dementia patients with motor neuron disease. 133 7

Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
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PMID:Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. 164 64

Several neurodegenerative diseases, including motor neuron disease (MND), are characterized by formation of abnormal cytoskeleton-derived inclusions which contain ubiquitin (Ubq). We have studied the distribution of Ubq in 26 cases of MND with light and electron microscopic immunocytochemistry. Ubiquitin-positive inclusions were found in neurons of anterior horns in most cases of amyotrophic lateral sclerosis (ALS) but were not present in other forms of MND. Ubiquitin immunoreactivity was observed in 10-15 nm intraneuronal filaments, which were not stained by antibodies to neurofilaments, and on dense bodies of dystrophic neurites throughout the neuropil of anterior horns and pyramidal tracts. Data analysis showed a trend toward lower percentage of Ubq-positive neurons in cases with longer duration of illness or lower number of neurons. A high percentage of Ubq-positive inclusions occurred in cases with an aggressive clinical course, suggesting that ubiquitination takes place at early stages of the disease.
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PMID:Ubiquitin in motor neuron disease: study at the light and electron microscope. 164 24

Monoclonal antibodies to ubiquitin were used in an immunocytochemical analysis of spinal cord from the Mnd (motor neuron degeneration) mouse, an animal model for motor neuron disease. Tissue from mice with mild, moderate and severe disease, from presymptomatic mice, and age-matched controls were analyzed. Ubiquitin deposits were observed in spinal neurons from presymptomatic animals and all stages of the disease. No immunoreactive deposits were observed in control mice at the concentration of the antibodies used. The presence of ubiquitin immunopositivity in presymptomatic spinal motor neurons suggests that ubiquitination might play a primary role in the pathogenesis of motor neuron disease in the Mnd mouse, and perhaps of motor neuron disease in general.
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PMID:Ubiquitin deposits are present in spinal motor neurons in all stages of the disease in the motor neuron degeneration (Mnd) mutant of the mouse. 165 91

Cells, including those of the nervous system, respond to damage by an increase in the synthesis of a family of proteins called 'stress proteins' which are amongst the most conserved gene products in evolution suggesting fundamental roles in cell metabolism. Stress-induced proteins have functions in normal cells, particularly for the importation of protein into membrane-limited organelles, and their up-regulation following stress is thought to be cytoprotective, by protecting proteins and organelles from damage. Ubiquitin is an important protein induced by cell stress. It is only found in nucleated cells and has several known functions; the most investigated being as a co-factor for the non-lysosomal intracellular degradation of abnormal or short lived proteins. Morphological studies using immunohistochemistry to localize ubiquitin protein conjugates have revealed that ubiquitin is a component of many of the filamentous inclusion bodies characteristic of neurodegenerative diseases, suggesting activation of a common neuronal response in this type of disease process. Immunohistochemical localization of ubiquitin conjugates has provided a new tool for the sensitive detection of such inclusions and has resulted in the identification of novel inclusion bodies in all cases of motor neuron disease. Preliminary work on enzymes involved in ubiquitin metabolism suggest that there are several possible mechanisms for the formation of inclusion bodies and may provide indirect evidence for the dynamics of inclusion body formation. Work in other areas of pathology indicate important roles for the stress proteins in immune surveillance and autoimmunity and it is likely that the general principles which are currently evolving will also have an impact in neuropathology.
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PMID:Ubiquitin, cell stress and diseases of the nervous system. 217 53

Involvement of Onuf's nucleus (ON) in 28 cases of amyotrophic lateral sclerosis/motor neuron disease (MND/ALS) with different clinical syndromes is reported. Although significant neuronal loss was absent, all cytoskeletal abnormalities typical of alpha-motor neurons in MND/ALS were found in ON. Spheroids were detected in 53.5% of cases; 0.6-4.5% of ON neurons contained Bunina bodies, which were present in 42.8% of cases. Ubiquitin-reactive inclusions (UBRI) of filamentous and hyaline type were found in 57.1% of cases and in 1.2-10.7% of ON neurons. Cases with pyramidal tract involvement (ALS) were involved by UBRI in 76.5%, whereas cases with progressive spinal muscular atrophy revealed the same inclusions in only 27.2%. No similar inclusions were present in sacral parasympathetic intermediolateral nucleus. It can be concluded, therefore, that ON belongs to the somatic motor system and is principally vulnerable to MND/ALS, albeit to a lower degree.
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PMID:Onuf's nucleus is frequently involved in motor neuron disease/amyotrophic lateral sclerosis. 760 28

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-protein conjugates have been identified in filamentous inclusions in various neurodegenerative disorders. In frontal lobe degeneration (FLD) no distinctive histological features have been reported with the exception of some ubiquitin-positive intraneuronal inclusions in cases associated with motor neuron disease. In the present study, we investigated five FLD cases without motor neuron disease using immunohistochemistry. A constant feature in all cases consisted of ubiquitin-positive neurites in layers I-III of the frontotemporal neocortex. These neurites were not argyrophilic, and could not be labelled with various antibodies against tau and neurofilament proteins. Ubiquitin-protein conjugates were found in distended dendritic branches, in dendritic spines and in smooth slender neurites, probably axons. No ubiquitinated neurites were seen in corresponding areas of the brain in aged controls. The nature of ubiquitinated proteins in FLD and the reason why they are confined to nerve cell processes is unknown but may be understood as part of an ongoing process leading to cell death observed in FLD.
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PMID:Frontal lobe degeneration: novel ubiquitin-immunoreactive neurites within frontotemporal cortex. 874 38

Histological and immunohistochemical findings in 20 cases of frontotemporal dementias-8 cases of dementia of frontal lobe type (DFT), 7 cases of Pick's disease (PD), and 5 cases of motor neuron disease with dementia (MND/D)-are presented. Common features of all three syndromes were: frontotemporal atrophy, involvement of subcortical nuclei, and swollen chromatolytic cells. Ubiquitin (Ub)-positive and tau-negative inclusions in cortical, hippocampal, and motor neurons were found in MND/D and DFT cases, suggesting a common pathogenesis of MND/D and DFT. MND/D showed the same cytoskeletal alterations in motor nuclei as MND without dementia: Bunina bodies and skein-like, Ub-positive inclusions. DFT differed from PD in the preponderance of histopathological changes in upper cortical layers, the sparseness of chromatolytic cells, and the absence of tau-positive Pick bodies (PBs). There were, however, two transitional cases showing Pick-type histology but no PBs, thus linking DFT and PD. PBs expressed chromogranin B and secretoneurin strongly, but chromogranin A only weakly. They were negative for the 70-kDa heat-shock protein, metallothionein, and glutathione-S-transferase.
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PMID:Different variants of frontotemporal dementia: a neuropathological and immunohistochemical study. 884 63


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