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)

We examined the presence of ubiquitin-immunoreactive skein-like inclusions (SLI) in the neostriatum and spinal cord in normal individuals and patients with different neurodegenerative diseases. Ubiquitin-immunoreactive SLI in the neostriatum were observed both in the normal individuals and in the patients with a variety of neurodegenerative diseases. In particular, SLI were frequently seen in normal aged subjects and certain neurodegenerative diseases, such as progressive supranuclear palsy and myotonic dystrophy. In contrast, the occurrence rate of SLI in cases with Pick's disease and multiple system atrophy tended to decrease. On the other hand, SLI in the spinal anterior horn were detected in cases of amyotrophic lateral sclerosis, but not in any cases with other neurodegenerative diseases. SLI in the neostriatum were also identifiable using phosphotungstic acid-hematoxylin and Gomori trichrome staining. Ubiquitin immunoelectron microscopy demonstrated that the SLI in the neostriatum corresponded to bundles of filaments. These features of SLI in the neostriatum were quite similar to those of intracytoplasmic rod-like inclusions (RLI) in the large neurons of caudate nucleus, which were first described by Kojima and Ogawa in 1974. Our findings indicate that SLI in the neostriatum are ubiquitin-related structures whose occurrence increases by aging, and less frequently accompany several neurodegenerative diseases, and are identical to at least some RLI.
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PMID:Ubiquitin-immunoreactive skein-like inclusions in the neostriatum are not restricted to amyotrophic lateral sclerosis, but are rather aging-related structures. 1091 19

Because transgenic mice expressing an altered stoichiometry of neurofilament proteins develop a motor neuron degeneration associated with neurofilamentous aggregate formation similar to that found in amyotrophic lateral sclerosis (ALS), we studied the expression of intermediate filament proteins in sporadic ALS. Archival cervical spinal cord paraffin-embedded sections from 11 disease and 11 control cases were studied by either in situ hybridization using 35S-labeled riboprobes or immunohistochemically using specific antibodies for the individual neurofilament subunit proteins, alpha-internexin, nestin, peripherin, vimentin, beta-actin, or Talpha1-tubulin. Median NFL, alpha-internexin, and peripherin steady-state mRNA levels were significantly reduced in the lateral motor neuron cell column (p < 0.05) of ALS cases, while neither NFM nor NFH mRNA levels were altered. ALS cases demonstrated an elevation of beta-actin mRNA levels (p < 0.01) with no increase in Talpha1-tubulin mRNA levels. No motor neuronal expression of nestin or vimentin was observed. Ubiquitin-immunoreactive perikaryal aggregates were immunoreactive for NFH or beta-actin, but not for peripherin, alpha-internexin, vimentin, or nestin. In contrast, neuroaxonal spheroids were strongly immunoreactive for NFH and peripherin, but not for beta-actin, alpha-internexin, vimentin, or nestin. These findings suggest that the stoichiometry of cytoskeletal protein expression in ALS spinal motor neurons is significantly altered in a pattern conducive to the formation of neurofilamentous aggregates.
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PMID:Characterization of neuronal intermediate filament protein expression in cervical spinal motor neurons in sporadic amyotrophic lateral sclerosis (ALS). 1108 75

This report concerns an autopsy case of atypical amyotrophic lateral sclerosis (ALS) with dementia mimicking frontal Pick's disease. The patient was a Japanese woman without hereditary burden who was 45 years old at the time of death. She developed abnormal behavior and amnesia at age 30, followed by disinhibition, aspontaneity, urinary incontinence, abulia, and rectal incontinence. Neurological signs compatible with ALS developed about 14 years after the disease onset. No respirator was used throughout the clinical course. Macroscopically, neuropathological examination showed atrophy of the frontotemporal lobes with accentuation in the convexities of the frontal lobes. Histologically, there was neuronal loss in the cerebral cortex, parahippocampal gyrus, amygdala, caudate nucleus, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to marked degeneration of the pyramidal tracts. Ubiquitin-immunoreactive neuronal inclusions were present in the frontotemporal cortical layer II neurons and motor neurons in the brain stem and spinal cord. In the hippocampal dentate granular cells, many ubiquitin-immunoreactive neurites were present without ubiquitin-immunoreactive intraneuronal inclusions. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS with dementia of long disease duration. We also note the possibility that motor neuron disease-inclusion dementia with a long clinical course may develop into ALS in the final stage of the illness.
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PMID:Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease: a report of an autopsy case with a clinical course of 15 years. 1151 92

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with circumscribed temporal atrophy. The patient was a Japanese woman without hereditary burden who was 71-year-old at the time of death. She developed dysarthria and gait disturbance at age 69, followed by dysphagia. A neurological examination about 1 year 11 months after the onset of the disease revealed absence of character change and of dementia. Neuroradiological examination disclosed circumscribed atrophy of the anterior part of the right temporal lobe. The patient died of respiratory failure 2 years after the disease onset. No respirator administration was performed throughout the clinical course. Macroscopically, neuropathological examination showed circumscribed atrophy of the right first temporal gyrus. Histologically, there was neuronal loss in the cerebral cortex, including the first temporal gyrus, the parahippocampal gyrus, subiculum, amygdala, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to loss of Betz cells, obvious degeneration of the pyramidal tracts, and the presence of Bunina bodies. Ubiquitin-immunoreactive intraneuronal inclusions were present in the hippocampal dentate granular cells, frontotemporal cortical layer II neurons, and motor neurons in the brain stem and spinal cord. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS without dementia, showing temporal lobe atrophy macroscopically, in addition to pathological hallmarks compatible with ALS with dementia. We also note the possibility that there is a forme fruste of ALS with dementia showing no overt dementia clinically.
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PMID:Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy: a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions. 1256 72

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder affecting adults. We studied the neuropathology and clinical correlations in 102 autopsy cases of ALS. The age at onset of the disease was significantly higher for the bulbaronset form (30 cases) than for the limb-onset form (72 cases). Dementia was confirmed in 7 cases. These 102 cases were divided into 4 pathological subgroups: typical ALS (59 cases), lower-motor-predominant ALS (23 cases), ALS with temporal lesions (18 cases), and ALS with pallido-nigro-luysian degeneration (2 cases). The age at onset was significantly higher for lower-motor-predominant ALS and ALS with temporal lesions than for typical ALS. In the lower motor neurons, Bunina bodies were detected in 88 cases, whereas ubiquitin-immunoreactive skein and/or spherical inclusions were detected in all 102 cases. Of the 100 available cases, 50 and 16 also showed ubiquitin-immunoreactive inclusions in the neostriatal and temporal small neurons, respectively. Ubiquitin-immunoreactive dystrophic neurites were also observed in the neostriatum in 3 of the 50 cases with neostriatal inclusions, and in the temporal cortex in 4 of the 16 cases with temporal inclusions. There was a significant association between the bulbar-onset form, temporal lesions, neostriatal inclusions and temporal inclusions, and between dementia, temporal lesions and temporal inclusions. Neostriatal and temporal dystrophic neurites were associated with dementia and bulbar-onset form through temporal lesions and temporal inclusions. The present findings may be helpful for designing further studies on the mechanisms underlying the development of ALS.
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PMID:Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. 1258 May 41

Between 1993 and 2001, we observed fifteen patients (ten men and five women, mean age 63 years) with frontotemporal dementia (FTD) which preceded signs of amyotrophic lateral sclerosis (ALS) which developed 21 months later. Mean disease duration in the fourteen deceased patients was 38 months. FTD associated with ALS is characterized by rapid course, predominance of disinhibited forms (orbito-basal), presence of aphasia with neologisms, and semantic memory disorders. Performed in all patients, single-photon emission computed tomography demonstrated a bifrontal pattern of low uptake, sometimes associated with low uptake in the anterior temporal region. In one patient, neuropathology revealed neuron atrophy and loss in the frontotemporal region, the anterior horns, and the hypoglossal nucleus. Ubiquitin-positive inclusions were visible in the dentate gyrus of the hippocampus and in the anterior horns. The dementia/ALS association is classically described is uncommon. It belongs to the FTD group since the Lund and Manchester consensus. Approximately 15 p.100 of patient with FTD can be expected to develop ALS. About 250 cases have been reported in the literature, half of them in the Pacific area where the incidence of ALS is high (55/100,000 inhabitants versus 1/100,000 in the rest of the world). Intermediary forms of FTD, semantic dementia, and progressive non-fluent aphasia are discussed since several cases of non-fluent progressive aphasia associated with ALS are reported in the literature. The links between these two degenerative diseases are discussed.
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PMID:[Neuropsychological and scintigraphic aspects of frontotemporal dementia preceding amyotrophic lateral sclerosis]. 1277 98

In the present study, we performed immunohistochemical techniques to investigate the changes in ubiquitin expression in the central nervous system of the transgenic mice expressing a human superoxide dismutase 1 mutation (SOD1)G93A. Sections of brains from control mice showed virtually no immunostaining for ubiquitin, whereas sections from SOD1G93A transgenic mice contained numerous granular or linear deposits of ubiquitin. A high density of the processes containing ubiquitin was detected all around the gray matter of the spinal cord of the mutant transgenic mice. Ubiquitin immunoreactivity was also detected in the cerebellum, brainstem and midbrain of transgenic mice. The first demonstration of the distribution of ubiquitin in the whole brains of the transgenic mice may provide clues for understanding the neuronal degeneration mechanism in amyotrophic lateral sclerosis and other neurodegenerative diseases.
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PMID:Immunohistochemical study on the aggregation of ubiquitin in the central nervous system of the transgenic mice expressing a human Cu/Zn SOD mutation. 1287 Feb 67

Amyotrophic lateral sclerosis with dementia (ALS-D) is a non-Alzheimer-type dementia characterized by both frontotemporal degeneration and motor neuron disease and marked by ubiquitin-positive, tau- and alpha-synuclein-negative intraneuronal inclusions and dystrophic neurites. New neuropathological diagnostic criteria for ALS-D are proposed on the basis of the present investigation of 28 autopsy cases. Clinical features included those of typical ALS-D, primary lateral sclerosis, atypical ALS with frontotemporal atrophy and atypical Pick's disease without Pick's bodies. Macroscopically anterior frontotemporal atrophy was observed involving or not involving the precentral gyrus. Microscopically non-specific neuronal loss and gliosis with spongiosis were seen, particularly in superficial layers II and III of the frontotemporal cortices. Diffuse fibrous gliosis was seen in the frontotemporal white matter. The substantia nigra and amygdala showed neuronal loss and gliosis. In all 28 cases, degeneration of both the lower and upper motor neuron systems, consistent with classic sporadic ALS, was present. The distribution and degree of degenerative frontotemporal lesions and motor neuron disturbance were of various patterns. Ubiquitin-positive and tau- and alpha-synuclein negative intraneuronal inclusions and dystrophic neurites in extramotor cortices were observed in all cases. Furthermore, ubiquitin-positive inclusions in lower motor neurons were found in all cases. The distribution pattern and density differed between neuronal inclusions and dystrophic neurites and correlated with clinicopathological phenotypes. Therefore, the ALS-D spectrum may be broader than that previously recognized, extending to primary lateral sclerosis, atypical ALS and to atypical Pick's disease without Pick bodies. Further investigation is needed to determine the characteristics of the ubiquitinated component in ALS-D.
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PMID:Amyotrophic lateral sclerosis with dementia: the clinicopathological spectrum. 1506 78

A 46-year-old patient developed amyotrophic lateral sclerosis (ALS) characterized by rapid progression. She needed respiratory assistance after a course of 9 months. She died 4.5 years after onset. Autopsy showed dramatic atrophy of the spinal cord, sparing only the posterior tracts, associated with neuronal loss and astrogliosis in various areas including the anterior horns, motor cortex, striatum, thalamus, and substantia nigra. Ubiquitin immunohistochemistry showed rare skein-like inclusions in the surviving spinal and medullary motor neurons. Eosinophilic inclusions were found in the nuclei of pyramidal neurons in the hippocampus. These inclusions were immunoreactive to antibodies against ubiquitin, promyelocytic leukemia gene product, proteasome, and ataxin-3. They were not immunoreactive to antibodies against tau, cystatin C, neurofilament, alpha-synuclein, SOD-1, and polyglutamine (1C2), and were not stained by ethidium bromide. Similar inclusions were found in the motor cortex. The immunoreactivity of the inclusions was similar to that encountered in diseases associated with CAG repeats, except for the negativity of the immunolabelling with 1C2. At the ultrastructural level, the nuclear inclusions were made of straight filaments (10-12 nm in diameter) arranged at random, reminiscent of the polyglutamine intranuclear hyaline inclusions.
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PMID:Amyotrophic lateral sclerosis with neuronal intranuclear protein inclusions. 1511 87

Frontotemporal lobar degeneration (FTLD) without tau pathology is clinically and pathologically heterogeneous. The present report describes the neuropathology of 52 brains with FTLD without tau pathology compared with 10 brains of amyotrophic lateral sclerosis (ALS) without dementia using ubiquitin immunohistochemistry. The 52 cases were classified into 47 cases of FTLD with motor neuron disease (MND)-type inclusions but without MND (FTLD-MNI), three cases of FTLD with MND (FTLD-MND), and two cases of dementia lacking distinctive histopathology (DLDH) based on the features of ubiquitin-immunoreactive (ubiquitin-ir) structures in the caudate, frontotemporal cortices and dentate fascia, and presence or absence of neuronal loss in lower motor neurons. Many ubiquitin-ir neuronal inclusions and neurites in the caudate nucleus, frontotemporal cortices, and ubiquitin-ir crescent-or ring-shaped neuronal inclusions in the dentate fascia characterized FTLD-MNI. Ubiquitin-ir neuronal intranuclear inclusions (NII) were observed in 26 of 43 cases and associated with many neurites in the caudate nucleus as well as a familial history in most cases. A subset of cases had Pick-body-like inclusions in the dentate fascia and caudate nucleus with paucity of neuritic pathology and no NII; another had crescent-shaped inclusions in the dentate fascia and neuritic pathology with NII in the caudate. FTLD with MND was characterized by a few or no ubiquitin-ir inclusions in the caudate nucleus and frontotemporal cortices and ubiquitin-ir granular inclusions in the dentate fascia, as well as loss of lower motor neurons. These features were similar to ALS, but different from FTLD-MNI. The findings suggest that FTLD-MNI has a different pathogenesis from FTLD-MND and ALS.
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PMID:Ubiquitin immunohistochemistry of frontotemporal lobar degeneration differentiates cases with and without motor neuron disease. 1631 57


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