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-immunoreactive (ub-ir) neuronal cytoplasmic inclusions are characteristically found in the extramotor cortex in patients with motor neuron disease and dementia (MND-dementia) and a subset of patients with frontotemporal dementia without motor symptoms (FTD-MND type). Recently, ub-ir neuronal intranuclear inclusions have been described in a small number of patients with familial FTD-MND type. To better define the sensitivity and specificity of this pathological change, we examined postmortem tissue from 14 patients with FTD-MND type (8 familial, 6 sporadic), 10 cases of MND-dementia (5 familial, 5 sporadic), and 19 cases of MND with no history of cognitive dysfunction (2 familial, 17 sporadic). Numerous intranuclear inclusions were found in multiple anatomic sites in 6/8 cases of familial FTD-MND. Rare intranuclear inclusions were present in the hippocampal dentate granule cells in 1 case of familial MND-dementia. No sporadic cases had intranuclear inclusions. These findings suggest that intranuclear inclusions are specific for familial FTD and may identify a subset of families with a common molecular pathogenesis. Although intranuclear inclusions are most characteristic of families in which the clinical presentation is pure FTD, they may also be found in some pedigrees with both FTD and MND; further supporting the hypothesis that FTD-MND type and MND-dementia represent a clinicopathological spectrum of disease.
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PMID:Neuronal intranuclear inclusions distinguish familial FTD-MND type from sporadic cases. 1273 60

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

Ubiquitin-positive tau-negative inclusions were initially described in the rare form of frontotemporal dementia (FTD) associated with motor neuron disease. However, recent studies have indicated that these inclusions are also present in typical FTD, which is usually characterized by nonspecific histological changes. To examine the contribution of these inclusions to neuronal loss and to explore their relationship with disease duration, we performed a quantitative immunocytochemical analysis of 38 typical FTD cases. Relationships between neuron and ubiquitin inclusion densities as well as between duration of illness and neuropathological parameters was studied using linear regression in both univariate and multivariate models. Ubiquitin-positive tau-negative intracytoplasmic inclusions were present in 65.8% of cases in the dentate gyrus, 57.9% in temporal cortex and 31.6% in frontal cortex. The highest densities of ubiquitin-positive inclusions were consistently observed in the dentate gyrus, followed by the temporal and frontal cortex. There was no statistically significant relationship between neuron and ubiquitin-positive inclusion densities in any of the areas studied. In contrast, ubiquitin-positive inclusion densities in the dentate gyrus were negatively related to the duration of illness. Our data suggest that the development of ubiquitin-related pathology is the rule and not the exception in typical FTD, yet is not causally related to neuronal loss. They also reveal that the development of ubiquitin-positive inclusion densities in the dentate gyrus may be associated with a more aggressive form of the disease.
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PMID:Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor neuron disease: a quantitative immunocytochemical study. 1517 May 77

Ubiquitin-immunoreactive (ub-ir) neuronal cytoplasmic inclusions are characteristically found in the extramotor cortex in patients with motor neuron disease (MND) and dementia (MND-dementia) and in a subset of patients with frontotemporal dementia (FTD) without motor symptoms (FTD-MND type). Recently, ub-ir neuronal intranuclear inclusions have been described in a small number of patients with familial FTD-MND type. To better define the sensitivity and specificity of this pathological change, we examined postmortem tissue from 14 patients with FTD-MND type (8 familial, 6 sporadic), 10 cases of MND-dementia (5 familial, 5 sporadic) and 19 cases of MND with no history of cognitive dysfunction (2 familial, 17 sporadic). Numerous intranuclear inclusions were found in multiple anatomic sites in 6/8 cases of familial FTD-MND. Rare intranuclear inclusions were present in the hippocampal dentate granule cells in 1 case of familial MND-dementia. No sporadic cases had intranuclear inclusions. These findings suggest that intranuclear inclusions are specific for familial FTD and may identify a subset of families with a common genetic basis. Although intranuclear inclusions are most characteristic of families with pure FTD, they may also be found in some pedigrees with both FTD and MND, further supporting the hypothesis that FTD-MND type and MND-dementia represent a clinicopathological spectrum of disease.
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PMID:Neuronal intranuclear inclusions distinguish familial FTD-MND type from sporadic cases. 1517 48

We report an autopsy case of dementia lacking distinctive histology (DLDH) showing semantic dementia. At age 47, a Japanese man developed aspontaneity, followed by semantic dementia a few months after the onset. Thereafter he developed disinhibition and the language disturbance, which progressed transcortical sensory aphasia and terminally mixed transcortical aphasia. At age 48, about 10 months after the disease onset, neurological examination revealed frontal signs and hyperreflexia in the four extremities and 4 months later, the patient presented with mild rigidity in the right upper and lower extremities. At age 49, 1 year and 8 months after the onset of the disease, he could not walk by himself. At age 50, 2 years and 8 months after the onset, he died of pneumonia. The brain weighed 1350 g. Macroscopically, atrophy of the frontal lobes and temporal lobes, predominant in the left, was evident. The caudate nucleus was severely atrophic, in addition to the depigmentation of the substantia nigra. Neuronal loss and astrocytosis was obvious in the cerebral cortex, prominently in the frontotemporal lobes, amygdala, caudate nucleus, putamen, pallidum, thalamus, and substantia nigra. In the caudate nucleus, prominent neuronal loss with fibrillary gliosis was obvious. Senile plaques, neurofibrillary tangles, Pick bodies, astrocytic plaques, and tufted astrocytes were not found by Gallyas and tau staining. Ubiquitin-immunoreactive intracytoplasmic inclusions were not encountered in the hippocampal dentate gyrus and superficial layers in the frontotemporal cortex. On the basis of meticulous perusal of the literature, we believe that our case is the first autopsy case of DLDH reported in Japan.
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PMID:[An autopsy case of dementia lacking distinctive histology showing semantic dementia]. 1591 59

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.
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PMID:Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family. 1596 97

Semantic dementia is a syndrome of progressive deterioration in semantic memory (knowledge of objects, people, concepts and words). It falls within the clinical spectrum of frontotemporal dementia but its pathology is yet to be studied systematically. This study included 18 consecutive post mortem cases meeting clinical criteria for semantic dementia. Clinic records and diagnostic histopathology were available for all cases; structural neuroimaging, neuropsychology and semi-quantitative histopathology/immunohistochemistry data were analysed where possible. The pathological diagnosis in a clear majority of cases was frontotemporal degeneration with ubiquitin inclusions (n = 13). Eleven of these cases had characteristic motor neuron disease-type inclusions in the dentate gyrus and cerebral cortex. Ubiquitin inclusions were found only in the inferior olivary nucleus in the other two, one of which was the only case to show degeneration of motor tracts and also to have shown evidence of motor neuron disease during life. None of the patients had motor symptoms or signs at presentation. A family history of motor neuron disease was documented in one case. Pick body-positive Pick's disease appeared three times. Two cases had Alzheimer's disease and significant coincidental Alzheimer-type pathology was also found in one of the ubiquitin inclusion cases. One of the Alzheimer's disease patients had changes in white matter signal on scanning, whereas all other scans showed cerebral atrophy only. Semi-quantitative assessment of regional neuronal loss found that anterior and inferior temporal regions bore the brunt of disease across all histopathological subtypes, usually on the left side, implicating this region in semantic processing.
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PMID:The pathological basis of semantic dementia. 1612 79

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

Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase the availability of free monomeric ubiquitin to the ubiquitin proteasome system (UPS) thus favoring protein degradation. Since mutations in the UCHL-1 gene, reducing UPS activity by 50%, have been reported in autosomal dominant PD, and UCHL-1 inhibition results in the formation of alpha-synuclein aggregates in mesencephalic cultured neurons, the present study was initiated to test UCHL-1 mRNA and protein levels in post-mortem frontal cortex (area 8) of PD and DLB cases, compared with age-matched controls. TaqMan PCR assays, and Western blots demonstrated down-regulation of UCHL-1 mRNA and UCHL-1 protein in the cerebral cortex in DLB (either in pure forms, not associated with Alzheimer disease: AD, and in common forms, with accompanying AD changes), but not in PD, when compared with age-matched controls. Interestingly, UCHL-1 mRNA and protein expressions were reduced in the medulla oblongata in the same PD cases. Moreover, UCHL-1 protein was decreased in the substantia nigra in cases with Lewy body pathology. UCHL-1 down-regulation was not associated with reduced protein levels of several proteasomal subunits, including 20SX, 20SY, 19S and 11Salpha. Yet UCHL-3 expression was reduced in the cerebral cortex of PD and DLB patients. Together, these observations show reduced UCHL-1 expression as a contributory factor in the abnormal protein aggregation in DLB, and points UCHL-1 as a putative therapeutic target in the treatment of DLB.
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PMID:Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies. 1638 Feb 64

We report a case of a right-handed 74-year-old man who showed semantic dementia with a disease duration of 19 years. He initially presented with excessive use of pronouns and semantic paraphasia at the age of 55 years. Impairment of object recognition developed 5 years after the onset. Face recognition impairment and stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years before death. Pathological examination disclosed circumscribed severe atrophy in not only the bilateral temporal tips but also in the left precentral gyrus and pars opercularis in a motor speech field. Pyramidal tract involvement and loss of Betz cells were also evident. On the other hand, neurons in the anterior horns and hypoglossal nuclei were spared in number, although astrocytes were mildly proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were present. These features clinically fit the international diagnostic criteria of semantic dementia and, histopathologically, frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). This case suggests that (1) the distribution of cortical lesions associated with language disturbance is not uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin pathology develop semantic dementia despite the high incidence of language disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND. After reviewing previous cases of FTLD-MND with a clinical course of more than 10 years, we also noticed that (3) FTLD-MND cases with a long disease duration often show upper motor neuron-predominant involvement.
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PMID:Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case presenting with semantic dementia and upper motor neuron signs with a clinical course of 19 years. 1701 98


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