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

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

Ubiquitin (Ub) is a small 76-residue protein, involved in intracellular protein degradation through a specific ATP-dependent system, which uses Ub as a tag to label proteins committed to be hydrolyzed by a specific 26 S protease. PGP-9.5 is another important component of the Ub system, i.e. a neuron-specific carboxyl-terminal hydrolase, which recycles Ub from Ub-polypeptide complexes. We have investigated the expression of Ub and PGP-9.5 in rat hippocampal neurons in an early phase of reperfusion in a model of transient global brain ischemia/hypoxia (bilateral occlusion of common carotid arteries for 10 min accompanied by mild hypoxia-15% O2-for 20 min), by means of immunohistochemical methods using light and electron microscopy. The intensity of Ub and PGP-9.5 immunoreactivity was evaluated by image analysis. We have detected a marked increase of Ub immunoreactivity (UIR) in neurons of CA1, CA2, CA3, CA4, and dentate gyrus subfields 1 hr after ischemia/hypoxia (but not after hypoxia only), statistically significant as confirmed by image analysis. Such increase in immunoreactivity in ischemic/hypoxic rats was localized essentially in the nuclei of hippocampal neurons. There were no changes in PGP-9.5 immunoreactivity. The data suggest that in the present model of rat brain ischemia/hypoxia Ub is involved in the neuronal stress response.
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PMID:Ubiquitin-mediated stress response in a rat model of brain transient ischemia/hypoxia. 902 69

Using in situ hybridization techniques with an RNA probe coding for approximately 3.5 repeats of ubiquitin, corresponding to the polyubiquitin genes, we were able to demonstrate that under normal conditions the expression of the ubiquitin genes predominates specially in regions CA1, CA2 and CA3 of the hippocampus, in the dentate gyrus and in Purkinje cells of the cerebellum, being less prominent in neuronal cell bodies of the cerebral cortex. When the animals were submitted to an acute oxidative stress by injection of Fe/Dextran, the hybridization signal was apparently increased in the above mentioned regions of the hippocampus and in the cerebral cortex. On the other hand, the animals chronically injected with Fe/Dextran showed a highly intense gene expression in the cerebral cortex and in the cerebellum, particularly in the granular cell layer of this structure. The hybridization signal of the transcripts was absent in the Purkinje cells. The results suggest that the expression of the ubiquitin genes by CNS neurons depends on the anatomical location of the cells and that it increases as a consequence of the oxidative stress conditions to which they are submitted.
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PMID:Expression of the ubiquitin genes in brain of normal and Fe/Dextran injected rats. 913 Feb 43

It has been suggested that dystrophic neurites in the hippocampal CA2-3 sector are characteristic of diffuse Lewy body disease (DLBD) but not of Parkinson's disease (PD). We investigated the severity of neuritic change in the CA2-3 sector of the hippocampus and in the periamygdaloid cortex (PAC) in 45 patients with clinically diagnosed and neuropathologically verified PD. Samples from amygdala, hippocampus, entorhinal cortex (ERC) and cortical gyri were examined for Alzheimer-type (AD) changes and Lewy bodies (LBs) using antibodies against ubiquitin and tau. Ubiquitin-positive but polyclonal tau-negative neurites were detected in the CA2-3 region of the hippocampus in 88% of patients and in the PAC in 91% of patients. The CA2-3 sector neurites correlated significantly only with LBs in all other brain areas, except in the amygdala. The neurites in the PAC correlated significantly with neuropathological variables in all other brain areas examined, except with tangles in the pre-central and frontal gyrus and with LBs in the amygdala and in the ERC. Unlike in the CA2-3 sector, the neuritic change in the PAC was more prominent in those PD patients with more severe cognitive impairment (P = 0.03). There was no significant correlation between the apoE4 allele load and the neuritic change in the PAC or in the CA2-3 sector. Our study revealed that cortical LBs and neuritic change in the amygdala and hippocampal CA2-3 sector co-exist in PD. Unlike hippocampal neurites, the PAC neurites are related to AD pathology. There seems to be a relationship between the PAC neurites and cognitive impairment in PD, but its significance needs further elucidation.
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PMID:Neuritic degeneration in the hippocampus and amygdala in Parkinson's disease in relation to Alzheimer pathology. 1044 55

We report a case of a 68-year-old right-handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22-month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side-predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin-positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin-positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau-positive bush-like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.
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PMID:Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: a non-demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala. 1802 74