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 (Ub), a stress protein thought to target abnormal proteins for degradation, is present in abnormal structures that occur in neuronal perikarya and axons of degenerative diseases including Alzheimer disease. To begin to assess the role of the Ub system in the axon, we studied expression and axonal transport of Ub and other stress proteins, as well as of Ub carboxyl-terminal hydrolase PGP 9.5, in the rat visual system in normal conditions and following heat-shock (HS). In the retina, both the constitutive and inducible forms of HSPs 70 were expressed under normal conditions, while in the superior colliculus the inducible form was detected only following HS. Ub, PGP 9.5 and HSPs 70 were transported in the axon exclusively with the slow component b (SCb), known to carry cytoskeletal and cytoplasmic proteins. The exceedingly long time needed for stress proteins to reach distant axonal locales at the rate of SCb (approximately 3 mm/day) makes it unlikely that they could contribute significantly to the stress response at those sites.
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PMID:Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5. 171 33

We report the autopsy findings of an 81-year-old patient with short-course sporadic amyotrophic lateral sclerosis lasting approximately 5 months. Pathological findings were probably very early. Light microscopy showed abundant eosinophilic Bunina type inclusions widely distributed not only in the motor neurons of the spinal cord and brain stem but also in neurons of the Onuf's and Clarke's nuclei. Fine structural study revealed that the inclusions seen in the Clarke's nuclei were identical to Bunina bodies observed in anterior horn cells. A direct connection between axonal swelling and perikaryon was often seen in the facial and hypoglossal nuclei and in the spinal cord. Ubiquitin-positive Lewy body-like inclusions and central chromatolysis-like changes were also found in the anterior horn cells.
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PMID:Widely distributed Bunina bodies and spheroids in a case of atypical sporadic amyotrophic lateral sclerosis. 205 68

Ubiquitin-immunoreactive structures in normal human brains ranging in age from 2 months to 91 years were studied with light and electron microscopy. Antibodies to ubiquitin immunostained structures in both neurons and glia. In the cerebrum, ubiquitin-immunoreactive, coarsely granular structures were most consistent with dystrophic neurites. They were most numerous in middle and upper cortical layers, especially lamina II of the entorhinal cortex and the cortical and accessory basal nuclei of the amygdala. Dystrophic neurites were first detected in brains of young adults, increased with age, and were numerous in the oldest brains. One of the normal elderly subjects had a small number of senile plaques with dystrophic neurites similar to those in the gray matter of the other brains, except for their location adjacent to amyloid deposits. With immunoelectron microscopy, dystrophic neurites were nonmyelinated neuronal processes containing dense, lamellar bodies, and finely granular material. White matter consistently had more immunoreactive structures than gray matter at all ages. The immunoreactive structures in white matter were smaller, less coarsely granular "dot-like" structures. With immunoelectron microscopy, dot-like structures were composed of dense inclusions within glial cells and focal swellings in myelin lamellae containing heterogeneous dense material. Only rarely were axons immunostained. Axonal spheroids in the basal ganglia, substantia nigra, and dorsal medulla were ubiquitin-immunoreactive. Spheroids were detected in these locations as early as the second decade, and they increased in number with age. A few dystrophic axons could be detected in spinal nerve roots of the oldest subjects. Other ubiquitin-immunoreactive structures included nuclei of small granular neurons, especially those in lamina II of the neocortex of the youngest brains; round cytoplasmic inclusions in tanycytes of all brains; and intranuclear Marinesco bodies in the substantia nigra and eosinophilic cytoplasmic inclusions in inferior olivary neurons in the oldest brains. These results demonstrate the spectrum of ubiquitinated structures in normal brains and suggest that progressive axonal dystrophy may be a more common age-related pathologic alteration of the brain than formerly recognized.
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PMID:Ubiquitin immunoreactive structures in normal human brains. Distribution and developmental aspects. 216 97

Ubiquitin targets proteins for attack by certain proteolytic enzymes, but the ubiquitinated cytoplasmic inclusions seen in some chronic neurodegenerative diseases may indicate the occurrence of reparative rather than destructive metabolic events. We have examined the production of ubiquitin in motor neurons of the rat's left hypoglossal nucleus after transection of their axons in circumstances that favour or prevent axonal regeneration. One week after axotomy, in situ hybridization with a radiolabelled cRNA probe revealed a twofold increase in the ubiquitin mRNA content of neurons with regenerating axons (nerve crushed) but not significant change when axonal regeneration had been prevented (nerve transected and ligated). After 2 weeks, ubiquitin mRNA was elevated to about 1.5 times the contralateral control level, regardless of the type of nerve injury, and by 4 weeks there were no longer any differences between the left and right sides. Despite the increased transcription, axotomy was not followed by any change in the quantity of ubiquitin-immunoreactive material in the nuclei or perikarya of hypoglossal neurons as measured by video image analysis of immunohistochemically stained sections. We suggest that ubiquitin is synthesized in neuronal cell bodies and transported into their axons, and that ubiquitin-mediated proteolysis is a metabolic process involved in the elongation of regenerating axons.
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PMID:Increased production of ubiquitin mRNA in motor neurons after axotomy. 789 20

Ubiquitin is a protein that targets proteins for non-lysosomal degradation. It has been found to be present in a number of inclusions characteristic of neurodegenerative diseases. Using the fluid percussion model of closed head injury in the cat, a well-established model of diffuse axonal injury (DAI), we now report that the reactive axonal swellings and the retraction balls produced in this model stain positively with anti-ubiquitin immunohistochemistry. Furthermore, the affected axons become ubiquitin positive quickly (within the first 6 h after injury). Anti-ubiquitin immunohistochemistry compares well with the recently reported ability of antibodies to low molecular weight neurofilament proteins to demonstrate reactive axonal change in DAI, and it could provide additional clues to the pathogenesis of axonal transection.
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PMID:Ubiquitin marks the reactive swellings of diffuse axonal injury. 838 48

We evaluated by immunohistochemistry the presence of beta-amyloid precursor protein (beta APP) and ubiquitin-like material which may accumulate in axons of the human spinal cord subjected to injury. Autopsy material was obtained from nine cases with different types of trauma: breech delivery with neonatal spinal injury, compression of the cord induced by fractures of the vertebral column, haematomas or intradural meningioma. The posttrauma period ranged from 10 days to several years. The spinal cord of six control cases without evidence of injury presented beta APP immunoreactivity in nerve cell bodies and in a few axonal profiles but not in dendrites. Seven of the nine cases with spinal cord trauma showed an accumulation of beta APP-immunoreactive material in axons of the longitudinal tracts at the site of the injury. Five cases presented similar axonal immunoreactivity in the grey matter of the cord. Ubiquitin-like immunoreactivity was present in expanded axons in cases with spinal cord injury. Cases with spinal cord trauma thus present beta APP-immunoreactive axons particularly of the longitudinal tracts in the same way as in trauma to rat spinal cord and in various brain injuries. The aggregation of beta APP-immunoreactive material indicates disturbed axonal transport of beta APP. Accumulation of ubiquitin-like immunoreactive material in expanded axons at the site of trauma may be one prerequisite for degradation of abnormal proteins by the ubiquitin-mediated proteolytic pathway.
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PMID:Accumulation of beta-amyloid precursor protein and ubiquitin in axons after spinal cord trauma in humans: immunohistochemical observations on autopsy material. 881 Nov 25

Two cases of Wernicke's encephalopathy with the rare phenomenon of ballooned neurons in the mamillary bodies are reported. Both patients suffered from acute Wernicke's symptoms starting approximately two weeks before death. The mamillary bodies contained grossly enlarged, ballooned neurons, in one case associated with focal necrosis. The affected neurons were immunoreactive for phosphorylated neurofilament (160 and 200 kDa), and synaptophysin. Ubiquitin and alpha beta-crystallin expression were not detected. The mamillo-thalamic tract appeared normal in both cases. There was a marked associated microglial reaction, as shown by the antibody Ki-MIP. It is concluded that the ballooning of mamillary neurons reflects an acute retrograde reaction to primarily axonal damage. Rather than being a rare manifestation of the disease, these cases may constitute a typical intermediate early stage (10-15 days) in the development of Wernicke's encephalopathy).
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PMID:Wernicke's encephalopathy with ballooned neurons in the mamillary bodies: an immunohistochemical study. 906 88

Protein gene product 9.5 (PGP 9.5) is a neuron-specific protein which acts as a ubiquitin carboxyl-terminal hydrolase. It facilitates the conversion of polyubiquitin to monoubiquitin, which can be reused for another catalytic cycle. Monoubiquitin plays an important role in degrading abnormal and denatured proteins. Previously, we have reported that ubiquitin-like immunoreactivity is expressed in axonal swellings following compression trauma to the rat thoracic cord. It was characterized by fast occurrence, progressive increase and gradual disappearance over a period of 9 days. The expression of PGP 9.5 has now been studied in the same material. Control rats showed a weak PGP 9.5 immunoreactivity in the nerve cell bodies of the cord. Except for the corticospinal tracts, the axons of other longitudinal tracts were weakly stained. Accumulation of PGP 9.5 immunoreactivity occurred in expanded axons at the site of compression already 4 h after trauma. They became more frequent in number 1 and 4 days after injury and remained so over the entire observation period of 9 days. The labelled axons were randomly distributed in the longitudinal tracts, but were never found in the corticospinal tracts. The extent of immunoreactivity was related to the degree of impact on the cord. Compression injury thus induces accumulation of both ubiquitin and PGP 9.5 immunoreactivity in axonal expansions. The injured axons may have a mechanism for degradation of proteins by the ubiquitin-mediated proteolytic pathway and another mechanism for effective ubiquitin regenerative cycling by the action of PGP 9.5.
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PMID:Expression of the ubiquitin carboxyl-terminal hydrolase PGP 9.5 in axons following spinal cord compression trauma. An immunohistochemical study in the rat. 920 Dec 40

We investigated the hippocampal pathology in diffuse Lewy body disease (DLBD) using alpha-synuclein immunohistochemistry. Ubiquitin-positive intrahippocampal structures caused by the degeneration of terminal axons of the perforant pathway were observed to be alpha-synuclein immunoreactive. These alpha-synuclein-positive degenerative terminals contained granulo-filamentous or vesiculo-tubular components similar to those of Lewy bodies (LB) immunoelectron microscopically, suggesting that alpha-synuclein may abnormally aggregate into filamentous or membranous cytoskeletal components including neurofilaments and synaptic vesicles in DLBD. A 'dying back' degenerating process due to a blockage of axonal transport may explain why the degenerative terminals and LB share similar alpha-synuclein-positive components, but the origin cells of the perforant pathway contain only a few LB.
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PMID:Degenerative terminals of the perforant pathway are human alpha-synuclein-immunoreactive in the hippocampus of patients with diffuse Lewy body disease. 987 32

The authors examined multiple brain sections from 15 autopsy cases of AIDS for the vascular changes, presence of amyloid plaques and signs of axonal damage. The mean patients age was 33.8 years (range 24-48 years). Neuropathological findings included: HIV-specific changes (5), opportunistic infections (7), lymphoma (1) and two cases with nonspecific changes. All sections were stained with hematoxylin-eosin (H-E), selected sections were stained with Masson trichrome, Gomori reticulin, Congo red and thioflavine S method. Two sections from each case were immunostained for the presence of beta-amyloid (4G8). ubiquitin, alpha-smooth muscle actin and CD31. The different forms of vascular changes were found in all cases. The common changes were: lymphocytic perivascular or transmural infiltrations and hyalinization, thickening or fibrosis of the arterial and arteriolar wall. The perivascular space widening up to status lacunaris was a frequent phenomenon in the basal ganglia and deep white matter. Some of the cortical arterioles formed little multiluminal structures. Immunohistochemical examination revealed features of hypertrophy of the vascular muscular layer and signs of the slight endothelial cells proliferation. In three cases 4G8 immunopositive. Congo red and thioflavine S-negative, diffuse beta-amyloid deposits were present in the gray matter, focally their localization was perivascular. Ubiquitin immunoreactivity presented as numerous dot-like structures or focal bundles of positive widened axons in the white matter, spheroids and scattered positive neurons were also found. The authors suggest that some of morphological changes within the brain and consecutive neuropsychological symptoms in AIDS are of the vascular origin. Presence of amyloid plaques and axonal damage are the elements of the complex degenerative and inflammatory process in the brain caused by chronic inflammatory stimulation in HIV infection.
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PMID:Vasculopathy and amyloid beta reactivity in brains of patients with acquired immune deficiency (AIDS). 1169 22


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