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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dissociated neuronal cultures from several regions of the nervous system elaborate two populations of neurites which have features of axons and dendrites. The microtubule-associated protein tau appears to segregate to the axon in some of these culture systems, however it does not do so until after the development of morphological polarity. Despite this observation, tau very likely has some role in the development of polarity because in cultured cerebellar macroneurons taken from the rat embryonic day 15 primordial cerebellum, the inhibition of tau expression by antisense techniques resulted in the failure of a single minor neurite to elongate and form an axon-like neurite. Tau antisense given continuously for up to 72 h kept neurons locked in a stage with minor neurites only; however when released from the effects of the antisense they fully recovered. The administration of tau antisense after the development of polarity resulted in the loss of the axon-like neurite, while dendrite-like neurites continued to grow. Together these results suggest that dendritic differentiation in cerebellar macroneurons requires the prior elaboration of an axon-like structure.
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PMID:Tau protein and the establishment of an axonal morphology. 166 96

The paired helical filament is the major fibrous component of neurofibrillary pathology in Alzheimer's disease. Over the last three years evidence has accumulated that the microtubule-associated protein tau forms an important, if not the sole, constituent of the paired helical filament. Tau protein in normal brain is bound to axonal microtubules by a tandem repeat region. In Alzheimer's disease a proportion of tau protein becomes abnormally phosphorylated and is no longer associated with axonal microtubules but instead accumulates in paired helical filaments throughout affected nerve cells. The tandem repeat region contributes substantially to the structural core of the paired helical filament, around which the amino-terminal half of the molecule forms a disordered coat.
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PMID:Tau proteins and neurofibrillary degeneration. 166 18

The ways in which the various microtubule-associated proteins (MAPs) contribute to cellular function are unknown beyond the ability of these proteins to modify microtubule dynamics. One member of the MAP family, tau protein, is restricted in its distribution to the axonal compartment of neurons, and has therefore prompted studies that attempt to relate tau function to the generation or maintenance of this structure. Sf9 cells from a moth ovary, when infected with a baculovirus containing a tau cDNA insert, elaborate very long processes. This single gene product expressed in a foreign host cell grossly alters the normal rounded morphology of these cells. The slender, relatively nonbranched appearance of these processes as well as their uniform caliber resembles the light-microscopic appearance of axons observed in several neuronal culture systems. Immunolabeling of the tau-expressing Sf9 cells demonstrated tau reactivity in the induced processes, and EM that microtubule bundles were present in the processes. Microtubule stabilization alone was insufficient to generate processes, since taxol treatment did not alter the overall cell shape, despite the induction of microtubule bundling within the cell body.
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PMID:Overexpression of tau in a nonneuronal cell induces long cellular processes. 167 91

The direct effects of the neurotransmitter serotonin on the catecholaminergic enzyme, tyrosine hydroxylase and the microtubule-associated tau protein were studied in a human neuroblastoma cell line. Undifferentiated LAN-5 cells, cultured in serum supplemented basal medium, or cells induced to differentiate by 6 day exposure to 10 uM retinoic acid were treated for 48 hr with 50 nM and 50 uM serotonin. In undifferentiated cells, serotonin treatment (50 uM) decreased both tyrosine hydroxylase activity and a 50 kD cytoplasmic fraction tau protein while 50 nM serotonin treatment caused this 50 kD protein to increase in the cytoplasmic fraction but decrease in the membrane fraction. While basal tyrosine hydroxylase activity increased in differentiated vs. undifferentiated cells, serotonin treatment had no effect on the enzyme or tau in differentiated LAN-5. This study shows serotonin to have direct effects on the biochemistry and cytoskeleton of undifferentiated cultured human neuroblastoma.
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PMID:Effects of serotonin on tyrosine hydroxylase and tau protein in a human neuroblastoma cell line. 168 52

Senile plaques (SP) in the cerebellum of 23 cases of Alzheimer's disease (AD), three with widespread amyloid angiopathy, were studied with a modified Bielschowsky stain and immunocytochemical methods using antibodies to a beta-amyloid synthetic peptide (beta ASP), phosphorylated neurofilament proteins, ubiquitin, tau protein, and glial fibrillary acidic protein (GFAP). The four subtypes of SP (diffuse plaques, compact plaques, perivascular plaques, and subpial fibrillar deposits) that were observed with the modified Bielschowsky stain were also stained with antibodies to beta ASP. Many cerebellar SP contained ubiquitin-positive granular elements resembling dystrophic neurites. In contrast to neuritic elements in cerebral SP in AD, ubiquitin-positive elements in cerebellar SP were not labeled with antibodies to phosphorylated neurofilament or tau proteins. Various degrees of glial reaction were observed in all subtypes of SP except diffuse plaques. The absence of phosphorylated neurofilament and tau epitopes in neuritic elements in cerebellar SP is not surprising since paired helical filaments have not been seen in the cerebellum. Nevertheless, our results suggest that cerebellar SP are frequently associated with dystrophic neurites.
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PMID:Modified Bielschowsky and immunocytochemical studies on cerebellar plaques in Alzheimer's disease. 168 24

Double-labeling immunohistochemistry was used to investigate the topographical relationship between beta-amyloid and tau protein epitopes present in cells bearing neurofibrillary tangles found in the hippocampal formation of patients with Alzheimer disease. An antiserum raised against the amino terminus of beta-amyloid stained numerous tangle-bearing cells and other bodies ("extracellular tangles"), but double labeling showed that the beta-amyloid staining is invariably peripheral to that of the tau-positive tangle proper. This and other results suggest that the extracellular amyloid plaques and the intracellular neurofibrillary tangles are biochemically distinct but may result from related pathological events that originate at the level of the nerve cell and lead to its degeneration.
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PMID:Topographical relationship between beta-amyloid and tau protein epitopes in tangle-bearing cells in Alzheimer disease. 169 27

A novel type of collagenous fibers has been isolated from human brain and characterized by electron microscopy and optical diffraction. It was found that the morphology of the fibers is similar, but not identical, to that of skin collagen. Also, the collagenous fibers show some similarities with the paracrystals that could be assembled in vitro from purified microtubule-associated protein tau. Immunological analyses indicated the presence of epitopes in these collagenous fibers which react with antibodies against collagen and tau.
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PMID:Collagenous structures present in brain contain epitopes shared by collagen and microtubule-associated protein tau. 169 58

The nature of senile plaques (SP) in the striatum in 14 cases of Alzheimer's disease (AD) was investigated with the modified Bielschowsky stain and immunohistochemistry using antibodies to a beta amyloid synthetic peptide, ubiquitin, tau protein, and paired helical filaments (PHF). Striatal SP, composed of beta amyloid deposits with or without neuritic elements, were demonstrated in all AD cases examined. Compact and perivascular amyloid deposits were concentrated in the ventral striatum, including the nucleus accumbens. Many diffuse amyloid deposits in the ventral striatum contained ubiquitin-positive granular elements, presumably representing dystrophic neurites, whereas most of those in the dorsal striatum did not have such elements. On the other hand, most compact amyloid deposits in both ventral and dorsal striatum had ubiquitin immunoreactivity. Dystrophic neurites with tau or PHF immunoreactivity were detected particularly around compact amyloid deposits. Our results indicate that the ventral striatum, which is closely affiliated with the limbic system, is frequently affected by amyloid deposits with dystrophic neurites, and suggest that the ventral striatum is particularly vulnerable to AD. Furthermore, our results suggest that amyloid deposits, especially compact deposits, may induce dystrophic neurites.
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PMID:Modified Bielschowsky stain and immunohistochemical studies on striatal plaques in Alzheimer's disease. 169 5

Tau protein is a major component of paired helical filaments (PHFs) which constitute the characteristic neurofibrillary tangle lesions observed in Alzheimer's disease. Two tau mAbs have been produced which show distinct patterns of immunoreactivity with intact human tau and with tau incorporated in PHFs. The mAb 423 recognises PHFs but not human tau on immunoblots whereas mAb 7/51 reacts with human tau but its epitope is buried within the PHF and is only exposed after formic acid treatment. A competitive ELISA has been developed for both of these mAbs and these have been used to quantify the two distinct tau epitopes in PHFs. Samples containing antigen are incubated with horseradish peroxidase-conjugated mAb at 4 degrees C for 16 h and non-adsorbed antibody then measured by binding, at 37 degrees C for 1 h, to a fragment of tau coated on microtitre plates. Bound enzyme-labelled antibody is measured kinetically using a spectrophotometer capable of automatically mixing the samples throughout a 2-min incubation with substrate and chromogen. The interfacing of the plate reader with a computer permits competitive curves to be plotted automatically using Softmax. Curves are fitted using a 4-parameter logistic algorithm which allows one to determine the relative immunoreactivity for different samples. The application of these assays to monitoring biochemical fractions and quantifying distinct immunochemical presentations of tau protein with these two mAbs is described.
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PMID:Competitive ELISA for the measurement of tau protein in Alzheimer's disease. 170 71

Neurofibrillary tangles (NFTs), a hallmark of Alzheimer disease, are commonly located in perikarya of neurons. In advanced cases of Alzheimer disease, however, NFTs are observed also in the extracellular space. As extracellular NFTs (E-NFTs), and occasionally intracellular NFTs (I-NFTs), are recognized by antibodies to beta-amyloid protein (beta AP), beta AP may be present not only in amyloid deposits but also in paired helical filaments (PHFs), the primary components of NFTs. We compared the antigenic characteristics of I-NFTs and E-NFTs with light- and electron-microscopic immunocytochemistry by using several antibodies to noncontiguous epitopes of the microtubule-associated protein tau and of ubiquitin (Ub) as well as an antiserum to beta AP. At variance with I-NFTs, E-NFTs were made predominantly of straight filaments (SFs), rather than PHFs, that were often separated by astroglial processes and in close association with small beta AP deposits. Occasionally, E-NFTs were made of bundles of amorphous material, which showed no resemblance to SFs, PHFs, or amyloid fibrils. The antigenic changes in E-NFTs suggest that when NFTs become extracellular they lose the N and, possibly, the C termini of tau while maintaining the intermediate region of the molecule; they also lose the N-terminal two-thirds of Ub while the C-terminal conjugation site of Ub is preserved. A small subset of E-NFTs reacted with antibodies to both beta AP and tau. Although in most E-NFTs, the epitopes recognized by tau and Ub antibodies were located in typical PHFs and SFs, the epitopes recognized in this subset of anti-beta AP and anti-tau-positive E-NFTs were located exclusively in the bundles of amorphous material. It is suggested that either beta AP epitopes are present but inaccessible in PHFs and SFs and become exposed after conformational changes occurring in the extracellular space or PHFs and SFs become closely associated with beta AP in the extracellular space.
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PMID:Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles. 170 17


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