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)

Two cases with classical clinical manifestations of progressive supranuclear palsy (PSP) showed severe progressive dementia as an additional clinical feature. Neuropathological study demonstrated typical features of PSP in the brainstem. Additionally, histological criteria of Alzheimer's disease (AD) were observed. A topographic and immunohistological study (with neurofilament subunit and Tau and Ubiquitin antibodies) of the distribution of neurofibrillary tangles (NFTs) was performed in order to compare the characteristics of NFTs from cortex and brainstem. NFTs from cortex were positive with all antibodies used and were predominantly distributed in cortical layers III and V and affected medium size neurons. Brainstem NFTs were positive only for neurofilament subunits and Tau. Cortical and brainstem NFTs showed immunohistological differences. Cortical NFTs in our two cases had a similar distribution as in control AD cases. On the basis of our observations we believe (1) that cortical tangles in our PSP cases are related to Alzheimer's disease and (2) that the cortical NFTs of PSP and AD are morphologically and immunohistologically distinct. Mechanisms concerned with the production of cortical and brainstem NFTs in PSP and AD are discussed.
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PMID:Clinical and pathological study of two patients with progressive supranuclear palsy and Alzheimer's changes. Antigenic determinants that distinguish cortical and subcortical neurofibrillary tangles. 132 66

Amyotrophic lateral sclerosis (ALS) patients with dementia were found to have ubiquitin-immunoreactive (IR) inclusions in the dentate granule cells of the hippocampus. These inclusions were also present in some patients with minor cognitive changes but otherwise typical ALS. Ubiquitin-IR inclusions were also found in neurons of superficial layers of the frontal and temporal cortex and in the entorhinal cortex in patients with ALS and dementia. These ubiquitin-IR inclusions were non-argyrophilic, and were not labelled by antibodies which identify Alzheimer's neurofibrillary tangles and Pick bodies, nor were they typical of cortical Lewy bodies. Our findings indicate that ubiquitin-IR inclusions in small neurons of the hippocampus, entorhinal area and neocortex are a characteristic feature of degeneration of non-motor cortex in ALS, and are particularly associated with cognitive impairment and dementia of frontal lobe type.
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PMID:Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia. 137 81

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

Ubiquitin immunocytochemistry with an antiserum which reacts with ubiquitin-protein conjugates demonstrates the presence of ubiquitinated proteins in filamentous inclusions found in neurones in the major human neurodegenerative diseases, i.e. Alzheimer's disease, diffuse Lewy body disease, motor neurone disease. Ubiquitin immunohistochemistry has revolutionized the neuropathological diagnosis of dementia showing that diffuse Lewy body disease is not, as previously supposed, a rare cause of dementia. The filamentous inclusions in neurones in the human neurodegenerative diseases can be divided into at least two types based on recent immunocytochemical studies. We have shown that a ubiquitin-carboxyl terminal hydrolase is present in Lewy bodies but not in neurofibrillary tangles in Alzheimer's disease. This observation is significant since it indicates that molecular pathological mechanisms in neurones in diffuse Lewy body disease are fundamentally different to Alzheimer's disease. Ubiquitin-protein conjugates are also found in vacuoles in areas of granulovacuolar degeneration in hippocampal neurones in Alzheimer's disease and in granulovacuoles in neurones of scrapie infected mouse brain. These locations suggest that ubiquitinated protein are present in the lysosome-related system of neurones. We have recently shown that ubiquitin-protein conjugates are indeed enriched some 12-fold in the lysosomes of normal fibroblasts and lymphocytes.
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PMID:The role of protein ubiquitination in neurodegenerative disease. 166 96

Ubiquitin, a protein thought to be involved in the ATP-dependent non-lysosomal degradation of abnormal proteins, has already been identified as a component of neurofibrillary tangles in Alzheimer's disease. We have examined ubiquitin immunoreactivity in a unique collection of brains from 16 ex-boxers including 11 with dementia pugilistica. Neurofibrillary tangles of dementia pugilistica were labelled with an affinity purified antiserum to ubiquitin, and BF10, a monoclonal antibody to a neurofilament epitope.
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PMID:Neurofibrillary tangles in dementia pugilistica are ubiquitinated. 185 Apr 50

Immunocytochemical and quantitative immunochemical techniques were used to study the expression of Alz-50 antigen, ubiquitin and Tau in neurologic disorders characterized by the formation of filamentous neuronal inclusions. Alz-50, anti-ubiquitin and Tau-1 immunostained the intraneuronal neurofibrillary tangles and the neuritic component of plaques, both in Alzheimer's disease and in the brains of patients without dementia, but extraneuronal tangles were largely unstained. These antibodies also reacted with Pick bodies, and with the neurofibrillary tangles of Kufs' disease and Guam Parkinsonism-dementia. In sections from the brain of a patient with progressive supranuclear palsy, virtually all of the tangles were immunostained with Tau-1 but only a few with Alz-50 or anti-ubiquitin. Anti-ubiquitin also labelled Lewy bodies and the inclusions of granulovacuolar degeneration. Quantitative analysis of immunoblots of homogenized frontal cortex showed significantly more Alz-50 antigen in the brains of patients with Alzheimer's and Pick's disease than in controls. The level of this antigen was increased both in the crude homogenates and in the cytosolic fraction. Ubiquitin immunoreactivity was increased only in the brains of patients with Alzheimer's disease and then only in the crude homogenates. The finding that antigenic determinants for Alz-50, anti-ubiquitin and Tau-1 are shared by several filamentous neuronal inclusions occurring in diverse neurologic disorders may reflect common metabolic defects underlying the formation of these inclusions, or common metabolic responses to their presence.
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PMID:Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. 283 88

Ubiquitin has been shown to be a component of neurofibrillary tangles in Alzheimer's disease. We now show immunocytochemically that it is also a component of neurofibrillary tangles in several other neurodegenerative diseases of diverse aetiology, including Down's syndrome, dementia pugilistica and postencephalitic parkinsonism, and in normal ageing. Ubiquitin immunoreactivity is not, however, generally found in the neurofibrillary tangles of progressive supranuclear palsy. These findings show that while associated ubiquitin is not a feature unique to the tangles of Alzheimer's disease, it is not simply a non-specific response to the presence of an inclusion body within the cell. The observations suggest that ubiquitin may have an important role in the formation of neurofibrillary tangles in a variety of neurodegenerative diseases.
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PMID:Ubiquitin is a component of neurofibrillary tangles in a variety of neurodegenerative diseases. 285 54

We compared the densities of lesions immunolabeled with ubiquitin, tau and beta A4 antibodies and stained by various silver impregnations, with the intellectual status. The densities of senile plaques and neurofibrillary tangles labelled by anti-ubiquitin antibody were correlated with the Blessed test score. Ubiquitin-positive neurofibrillary tangles were less numerous than those labelled by Gallyas, anti-tau, Bodian's and Bielschowsky's methods. There were five times more beta A4 deposits than ubiquitin positive plaques. beta A4 deposits could be numerous in cases in which ubiquitin immunolabelling was entirely negative. Bielschowsky's method, silver methenamine and thioflavin S revealed more senile plaques than anti-ubiquitin, whereas anti-tau, Gallyas', Bodian's and Cross' techniques revealed similar numbers. Anti-ubiquitin positive lesions were correlated with the severity of dementia. Compared with other staining methods, sensitivity of anti-ubiquitin was weaker for neurofibrillary tangles than for senile plaques. These findings suggest that ubiquitin epitopes are linked to the neurofibrillary changes (in the perikaryon or within the senile plaques), and are absent from beta A4 deposits, either diffuse or compact.
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PMID:Alzheimer's lesions labelled by anti-ubiquitin antibodies: comparison with other staining techniques. A study of 15 cases with graded intellectual status in ageing and Alzheimer's disease. 769 67

The topographic distribution of degenerative changes in large brain sections from five sporadic amyotrophic lateral sclerosis (ALS) patients with dementia and three without dementia was examined. The dementia characteristics were impaired shifting from one line of thinking to another, perseveration, and emotional disinhibition as well as impairment of cognition, and judgment. Neuropathological examinations showed definite ALS changes in all the patients studied. In addition, the five patients with dementia showed neuronal loss, gliosis, and sponginess of the superficial layers throughout the cerebral cortices, predominantly in the dorsomedial cortex of the temporal tip and the parahippocampal, ambiens, anterior cingulate, rectal, orbital, and insular gyri as well as neuronal loss in the basolateral nucleus of the amygdala, nucleus accumbens, and subiculum of the hippocampus. Ubiquitin-immunoreactive inclusions were present in some neurons in the granular cell layers of the hippocampus. Fibrous gliosis was extensive in the subcortical and deep white matter of the frontotemporal lobes. The affected regions take in the limbic system and its associated areas which are the sources of the psychological problems, including emotional disturbance, experienced by these ALS patients. The psychological problems of ALS need to be investigated in relation to the involvement of the limbic system.
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PMID:Participation of the limbic system and its associated areas in the dementia of amyotrophic lateral sclerosis. 783 49

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


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