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)

Amino acid sequencing of a CNBr digest of the tau protein isolated from bovine brain revealed an amino acid sequence of 17 residues, Pro-Gly-Leu-Lys-Glu-Ser-Pro-Leu-Gln-Ile-Gly-Ala-Ala-Pro-Gly-Leu-Lys, which we call peptide I, with heterogeneity at position 11 of glycine (peptide Ia) and proline (peptide Ib); peptide I showed no homology with the previously reported cDNA-derived mouse and human tau sequences. Antisera raised to synthetic peptides corresponding to peptides Ia and Ib labeled all the bovine tau polypeptides recognized by other monoclonal and polyclonal antibodies to bovine tau. Antisera to peptide Ib did not label any mouse tau polypeptides; however, an anti-Ia antiserum labeled two of the four mouse tau polypeptides. Antisera to both peptides labeled paired helical filaments (PHF) as neurofibrillary tangles, plaque neurites, and neuropil threads in Alzheimer disease brain and PHF polypeptides on immunoblots. Immunostaining with anti-Ia antisera of PHF in tissue sections and PHF polypeptides, but not bovine tau, on immunoblots was markedly increased when pretreated with alkaline phosphatase. These studies suggest that (i) the amino acid sequences of some isoforms of tau peptide might be different from that predicted from cDNAs, (ii) a tau peptide that is absent in the predicted sequences is present in PHF in Alzheimer disease, and (iii) tau in PHF is abnormally phosphorylated.
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PMID:Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease. 250 95

In a previous report we have shown that microtubule-associated protein tau can be induced to form paracrystals (Lichtenberg, B., E.-M. Mandelkow, T. Hagestedt, and E. Mandelkow. 1988. Nature [Lond.]. 334:359-362). A striking feature was the high degree of elasticity of the molecules. We now report that this property is related to the state of phosphorylation. When tau is dephosphorylated by alkaline phosphatase, it becomes shorter and more elastic; when it is phosphorylated by Ca++/calmodulin-dependent kinase, it becomes longer and stiffer. This may provide a model for the control of structural properties of tau-like molecules by phosphorylation.
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PMID:Tau protein becomes long and stiff upon phosphorylation: correlation between paracrystalline structure and degree of phosphorylation. 250 54

A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to tau, electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to tau-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF.
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PMID:Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. 308 67

Microtubule-associated protein tau was characterized in 5 Alzheimer and 5 control brains using two monoclonal antibodies, Alz 50 and Tau-1. Quantitative analysis of immunoblots with the antibodies showed that both homogenate and supernatant fractions (12,000 x g) from Alzheimer brains contained 38-65% less tau immunoreactivity compared to normal brains. The reduction was found in all brain regions studied (frontal and temporal lobes and thalamus) and in both gray and white matter. In partially purified tau preparations, the yield of protein was lower in Alzheimer (by 35%) than in control brain. Incubation of brain proteins, transferred onto nitrocellulose paper, with alkaline phosphatase had either no effect or slightly increased the antibody binding to tau proteins from both brain tissues. Immunoblots of tau-enriched preparations subjected to two-dimensional gel electrophoresis showed no major changes in the staining pattern of tau isoforms in Alzheimer samples except for a weaker reactivity of the basic isovariants as compared to non-Alzheimer samples. The elution volume of tau from Alzheimer brain supernatant on a Sepharose CL-6B column was similar to that from non-Alzheimer brain and equal to that of aldolase (Mr = 158,000). Our data suggest that most of tau proteins from both types of brain have similar biochemical properties. The reduction in tau reactivity in Alzheimer tissue may be due to a reduction in neuronal cell population or incorporation of soluble tau into stable structures such as neurofibrillary tangles, since the tangles have been shown to react with anti-tau antibodies.
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PMID:Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz 50 and Tau-1. 313 34

Induction by nerve growth factor of neurite outgrowth in PC12 cells is transcription-dependent and is associated with the accumulation of tau protein. It was recently shown that short-term treatment with staurosporine, a protein kinase alkaloid inhibitor, induced an elevation of tau protein levels and outgrowth of stable neurites. In this study, we analyzed the mechanism(s) by which nerve growth factor and staurosporine exert their effects on tau levels. We demonstrate that nerve growth factor affects tau mRNA stability, thus contributing to the observed increase in tau mRNA levels. On the other hand, tau mRNA levels were not affected by the treatment with staurosporine. We also demonstrate that the phosphorylation of tau protein was reduced after treatment of PC12 cells with nerve growth factor or staurosporine, as shown by immunoblot analysis using specific antibodies and alkaline phosphatase treatment. Thus, regulation of tau levels by nerve growth factor appears to be mediated by transcriptional, post-transcriptional and posttranslational steps, whereas the effect of staurosporine on tau levels may be attributed to its effect on the state of phosphorylation of the protein.
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PMID:Short- and long-term mechanisms of tau regulation in PC12 cells. 759 25

Neurofibrillary tangles in Alzheimer's disease have been previously found to be labeled by some neurofilament antibodies that also recognize tau proteins. We have studied the reactivity of two such monoclonal antibodies, RT97 and 8D8, and of an anti-ubiquitin serum with the abnormal paired helical filaments (PHF)-tau (A68) polypeptides known to be the main component of the PHFs constituting the neurofibrillary tangles. 8D8 recognized the three major PHF-tau polypeptides, but RT97 reacted only with the two larger PHF-tau species. PHF-tau polypeptides were labeled by 8D8 and RT97 much more strongly than normal human tau and this labeling was decreased after alkaline phosphatase treatment. Anti-ubiquitin and anti-phosphotyrosine antibodies did not label PHF-tau polypeptides. The immunoreactivity of proteolytic fragments of PHF-tau polypeptides was studied with RT97, 8D8, and a panel of tau antibodies. The epitope for 8D8 on PHF-tau was localized between amino acids 222 and 427 in the carboxyl half of tau. The RT97 epitope on PHF-tau was localized in the amino domain of tau, probably in the 29-amino-acid insertion (insert 1) found towards the amino terminus of some tau isoforms. These results show that the basis for the labeling of neurofibrillary tangles by antibodies 8D8 and RT97 to neurofilament is their ability to react with PHF-tau polypeptides by recognizing sites specifically modified on PHF-tau, including a site specific to some tau isoforms.
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PMID:Neurofilament monoclonal antibodies RT97 and 8D8 recognize different modified epitopes in paired helical filament-tau in Alzheimer's disease. 768 Nov 1

Two monoclonal antibodies C5 and M4 raised against Sarkosyl-insoluble paired helical filaments (PHF) specifically labeled fetal tau, but hardly labeled normal adult tau. C5 immunoreactivity was eliminated by alkaline phosphatase treatment at 37 degrees C, whereas M4 reactivity could be removed only by the treatment at 67 degrees C. Epitope analysis showed that C5 and M4 recognition sites are in residues 386-406 and 198-250, respectively, according to the numbering of the longest human tau isoform. Thus, the phosphorylation sites are located in the amino- and carboxyl-terminal portions of the microtubule-binding region. These two well-characterized monoclonals should be valuable in the identification of a protein kinase(s) that converts normal tau into PHF-tau.
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PMID:Characterization of two distinct monoclonal antibodies to paired helical filaments: further evidence for fetal-type phosphorylation of the tau in paired helical filaments. 768 67

Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of tau proteins. These cells contained mainly a form of tau comparable to fetal brain tau in molecular weight (55 kDa). Neuroblastoma tau reacted with antibodies that recognize epitopes spanning the whole tau molecule (E-1, Alz50, Tau-1, and Tau46), and antibodies (PHF-1, NP8, and T3P) that recognize hyperphosphorylated tau (PHF-tau) in Alzheimer's disease (AD) brains. Exposure of the cells to 45 degrees C heat stress resulted in dephosphorylation of the epitopes recognized by PHF-1, NP8, and T3P. Transfer of the heat-stressed cells to 37 degrees C led to rephosphorylation of the dephosphorylated epitopes. Cells that had been treated with okadaic acid (OA), regardless of whether they were subsequently subjected to heat stress or heat stress and recovery, all contained tau with a molecular weight similar to that of control cells. These tau proteins, similar to tau in control cells, also reacted with antibodies to phosphorylated epitopes. However, unlike the tau from control or heat-stressed cells, the OA-treated and heat-stressed tau had decreased reactivity with Tau-1. Alteration of Tau-1 immunoreactivity has been reported to be an early event in AD neurodegeneration. The reduction of Tau-1 immunoreactivity observed in OA-treated samples could be restored by incubation of electroblots of isolated tau with alkaline phosphatase, indicating an induction of the Tau-1 epitope phosphorylation by OA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversible heat stress-related loss of phosphorylated Alzheimer-type epitopes in Tau proteins of human neuroblastoma cells. 769 94

In Alzheimer's disease, paired helical filaments composed mainly of abnormally phosphorylated tau accumulate in certain selected neurons of the brain, and microtubules are rarely seen in the affected cells. In the present study, the binding of 32P-labeled 8-azidoguanosine triphosphate ([gamma-32P]8N3GTP), the photoaffinity analogue of GTP to the beta-subunit of tubulin in brain homogenates was found to be markedly lower in patients with Alzheimer's disease than in aged control human cases. No significant differences were observed in the levels of the alpha- and beta-subunits of tubulin between Alzheimer's disease and control brains obtained 2-7 h postmortem. In nine of 19 Alzheimer's disease and 11 of 12 control autopsied brains (2-7 h postmortem and stored at -75 degrees C) tubulin was isolated successfully from brain cytosol by in vitro polymerization induced with DEAE-dextran. The GTP binding was observed in the two cycled assembled microtubule preparations from all the normal control, and in eight of nine Alzheimer's disease cases. Alzheimer's disease microtubule preparations contained varying amounts of abnormally phosphorylated tau, whereas no abnormal tau was detected in the control brain preparations. Addition of bovine tau to bovine, normal human, and Alzheimer's disease brain tubulin preparations markedly increased GTP binding to the beta-subunit. An alkaline phosphatase-treated paired helical filament-enriched preparation increased by approximately twofold the GTP binding to bovine brain tubulin. GTP binding to tubulin prepared by phosphocellulose chromatography of two cycled microtubules from three Alzheimer's disease and three normal control brains, revealed insignificant differences between the two groups. These findings have suggested that (1) tau protein promotes the GTP binding to the beta-subunit of tubulin, and (2) the breakdown of the microtubule system in brains of patients with Alzheimer's disease might in part be due to the abnormal phosphorylation of tau which depresses the GTP binding.
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PMID:Guanosine triphosphate binding to beta-subunit of tubulin in Alzheimer's disease brain: role of microtubule-associated protein tau. 783 71

In a normal mature neuron, microtubule associated protein tau promotes the assembly of tubulin into microtubules and maintains the structure of microtubules. In Alzheimer disease brain, tau is abnormally hyperphosphorylated and is the major protein subunit of paired helical filaments (PHF). In the present study, the biological activity of tau in PHF and the effect of dephosphorylation on this activity were examined. PHF were isolated from Alzheimer disease brains and tau from the untreated or alkaline phosphatase-treated PHF was extracted by ultrasonication in microtubule assembly buffer. Tubulin was isolated by phosphocellulose chromatography of three cycled microtubules from bovine brain. PHF-tau did not promote assembly of bovine tubulin into microtubules whereas tau from the dephosphorylated PHF produced a robust microtubule assembly. These studies suggest (i) that in Alzheimer disease tau in PHF is functionally inactive because of abnormal phosphorylation and (ii) that the abnormally phosphorylated site(s) in PHF that inactivates PHF-tau is accessible to enzymatic dephosphorylation in vitro.
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PMID:Alzheimer paired helical filaments. Restoration of the biological activity by dephosphorylation. 804 85


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