Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microtubule-associated protein tau, and the cytoplasmic protein ubiquitin, are constituents of pathological neurofibrillary tangles found in Alzheimer's disease. In order to see if there is any physiological relationship between these proteins in a functioning human system, human neuroblastoma (LAN-5) cells were grown in vitro and differentiated to a neuronal phenotype. Cell extracts were analyzed by SDS-PAGE, immunoblot, and immunoprecipitation techniques. The colocalization of ubiquitin and tau immunoreactivity was noted in 12- and 35-kDa bands, predominantly located in a cell membrane fraction. The bands were also isolated by immunoprecipitation with the Alz-50 antibody and then identified with a ubiquitin antiserum. These findings show a relationship between tau and ubiquitin in a human neural cell line. This interaction suggests that tau may normally be degraded by an ubiquitin-dependent mechanism and alterations in it may contribute to the formation of neuro-fibrillary pathology.
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PMID:Tau-ubiquitin protein conjugates in a human cell line. 172 70

Abnormal neurites, neuropil threads, are a widespread and characteristic lesion of Alzheimer's disease likely to play a major role in the cognitive impairment of this disease. Contrary to normal neurites, neuropil threads contain straight and paired helical filaments that contain the microtubule-associated protein tau and ubiquitin. It is not known whether these abnormal filaments are added to or replace the normal cytoskeleton. In this study, we examined the fine structure of neuropil threads and carried out a morphometric analysis of the neurofilaments and abnormal filaments contained in the neuropil threads by using an antiserum to tau and colloidal gold immuno-electron microscopy. Almost 70% of the neuropil threads contained straight or paired helical filaments with no neurofilaments. The total number of filaments in each neuropil thread remained essentially unchanged either when straight or paired helical filaments were present alone or when they coexisted either together or with neurofilaments. When the three types of filaments were expressed as a proportion of the total, a linear inverse correlation was found between neurofilaments and straight filaments as well as between straight and paired helical filaments. Approximately 10% of the neuropil threads were found to be myelinated axons. It is concluded that straight filaments are likely to replace neurofilaments, that they in turn might be replaced by paired helical filaments, and that this process occurs in axons as well as dendrites.
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PMID:Neuropil threads of Alzheimer's disease show a marked alteration of the normal cytoskeleton. 190 81

This investigation concerns the expression of paired helical filaments, tau protein, ubiquitin, beta-amyloid protein, and synaptophysin in the hippocampus of patients with parkinsonism-dementia complex on Guam (PDC) and Alzheimer's disease. Alzheimer's neurofibrillary tangles (NFTs) were identified in all cases of PDC and Alzheimer's disease by the modified Bielschowsky method, with which they were readily detected, and by immunohistochemical procedures using antibodies to paired helical filaments, tau protein, and ubiquitin. Observations regarding the different morphological stages indicated that NFTs were similar in PDC and Alzheimer's disease. The same markers were also useful for detecting neuropil threads, abundant in the CA1 field and the subiculum in both diseases. In the CA4 region of some PDC cases, prominent threads were noted. No senile plaques or amyloid angiopathies were seen in the hippocampus of the PDC cases examined. There was a significant decrease in synaptophysin immunoreactivity, most pronounced in the subfield CA1 and the subiculum, as well as in the outer molecular layer of the dentate gyrus, in both disorders.
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PMID:Immunohistochemical study of the hippocampus in parkinsonism-dementia complex on Guam. 195 65

The main pathological features of Alzheimer's disease are Alzheimer neurofibrillary tangles and senile plaques. Recent biochemical research revealed that tangles are composed of tau protein and ubiquitin and amyloid in senile plaques is composed of beta protein which is a fragment of the membrane receptor protein. Although fraction, other data suggest that whole molecules become abnormal and aggregate into PHF. On the other hand, beta protein is a small cleavage product of the precursor protein. It is not concluded yet whether abnormal precursor proteins exist or not. Recent research in this field is reviewed.
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PMID:[Tau protein and beta protein]. 212 Apr 89

We studied the topographic distribution and immunohistochemical characteristics of spinal cord neurofibrillary tangles (NFTs) in 6 patients with Guamanian amyotrophic lateral sclerosis (ALS) and 6 patients with parkinsonismdementia complex (PD) on Guam, using antibodies to tau protein and ubiquitin. The NFTs were immunoreactive with both antibodies, but staining for tau was more pronounced. As identified by this reactivity, all the Guamanian ALS and PD cases examined showed spinal cord NFTs. The posterior horn had the most and the anterior horn the least. In the posterior horn the NFTs were located mainly in the marginal areas. Large anterior horn cells showed few, if any, NFTs. In addition to perikaryal NFTs, we observed tau-reactive neurites. Our results provide evidence that spinal cord NFTs are not uncommon in Guamanian ALS and PD on Guam and that they are more numerous than previously found with conventional methods.
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PMID:Spinal cord neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex: an immunohistochemical study. 216 Oct 95

An antigenic profile of subcortical and cortical Lewy bodies was determined in the presence or absence of neurofibrillary tangles in the same brain using antisera and monoclonal antibodies to various cytoskeletal elements as well as to determinants not present in the normal cytoskeleton. The cores of many Lewy bodies were strongly reactive with a monoclonal antibody to paired helical filaments which has been shown to recognize ubiquitin. This antibody also stained Marinesco bodies in the same tissue sections. Two monoclonal antibodies to phosphorylated epitopes of neurofilament proteins (SM I 31, SM I 34) stained the peripheries of about 40% of all discernable Lewy bodies on untreated paraffin sections. Reactivity with a monoclonal antibody to neurofilaments (SM I 33) appeared only after pretreatment of the sections with phosphatase. Lewy bodies did not bind antibodies to tau protein. Our results show that, as previously shown for neurofibrillary tangles, Lewy bodies also contain ubiquitin. The uncovering of neurofilament epitopes by treatment with phosphatase indicates that abnormal phosphorylation of cytoskeletal elements may play a role in the pathogenesis of the Lewy body.
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PMID:An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. 246 24

The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal changes in the process of tangle formation. Exposure of certain ubiquitin epitopes in the pathological fibers may reflect an unsuccessful attempt of proteolytic degradation.
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PMID:Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. 249 52

The antigenic components of Lewy bodies in the cerebral cortex and substantia nigra in 5 cases of diffuse Lewy body disease were examined by immunocytochemistry, using antibodies to neurofilaments (in the phosphorylated or non-phosphorylated forms); to ubiquitin; to the microtubule-associated proteins MAP1, MAP2 and tau; to isolated Alzheimer paired helical filaments, and to tubulin, in the tyrosinated and non-tyrosinated forms. Immunoreactivity with antibodies to cytoskeletal components was identical to that previously described for Lewy bodies of idiopathic Parkinson disease, with the exception that the inclusions of diffuse Lewy body disease (in both cortex and substantia nigra) were stained by an antibody to tau protein. Our findings indicate that although the inclusions found in diffuse Lewy body disease share structural and epitopic features with the inclusions of idiopathic Parkinson disease, they also have distinguishing characteristics (in addition to the differing neuronal populations involved). Also, they suggest that although the inclusions in both conditions appear similar, they probably have different pathogenetic origins.
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PMID:The presence of tau distinguishes Lewy bodies of diffuse Lewy body disease from those of idiopathic Parkinson disease. 254 30

Brains were obtained at autopsy from 24 patients with Down's syndrome, ranging in age from 13 to 71 years. Neurofibrillary tangle containing neurones of the hippocampus were stained using a Palmgren silver method and immunocytochemically (PAP) using antisera to paired helical filament protein, human tau protein and ubiquitin, as primary antibody. Counts of cells stained by each method were compared. In patients under 50 years of age, in whom only a limited number of tangle bearing cells were present, the number of profiles visualized with silver, anti-paired helical filament and anti-tau methods were similar. However, in patients over 50 years of age (and in certain of those under 50), in whom numerous tangles were present, the number of cell profiles visualized with silver and anti-paired helical filament methods were still similar though anti-tau detected fewer positive cells. This was because of the increased presence, in such patients, of extracellular tangles which had "lost" anti-tau immunoreactivity. Such data suggest that although tau protein forms a major antigenic determinant of neurofibrillary tangles in Down's syndrome (as it does in Alzheimer's disease) this protein may only decorate the basic paired helical filament protein skeleton, and is removed by macrophagic activity upon neuronal death. In all patients, anti-ubiquitin revealed fewer tangles than any other method. It is possible that ubiquitin may be present only transiently, within tangles perhaps following initial formation and lasting only as long as the normal protein degradation processes remain viable within the diseased neurone.
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PMID:Immunocytochemical profile of neurofibrillary tangles in Down's syndrome patients of different ages. 255 74

In his original 1911 publication Alois Alzheimer classified neurofibrillary tangles (ANT) into three morphologically defined subgroups according to their stage of maturation. The present study shows that changes in the morphological appearance of ANT during their maturation process are accompanied by changes in their antigenic profile. As shown by several immunocytochemical studies these abnormal phosphorylated microtubule-associated protein tau and of ubiquitin. In this study, immunoreactivity for the altered tau is not only seen in a subset of tangles but also in the cytoplasm of some nerve cells lacking ANT, which we believe to be at a stage of neuronal alteration preceding the formation of compact tangles (Stage 0 tangles). Similar numbers of Stage 0 tangles are present in the brains of age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls lacking ANT. In extracellular "ghost tangles", the ultimate stage of neurofibrillary degeneration, immunoreactivity for tau is accessible to antibodies only when tissue sections are pretreated with formic acid to uncover the binding sites. In contrast to tau, presence/accessibility of an epitope residing on residues 50-65 of ubiquitin recognized by a monoclonal antibody raised to paired helical filaments (3-39) increases during the maturation of ANT and is most pronounced in "ghost tangles". Appearance/uncovering of the 3-39 epitope and masking of tau reactivity during tangle maturation may reflect degradation or conformational changes in the pathological filaments due to their aging and the final loss of their parent nerve cells.
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PMID:Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles. 255 44


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