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

The fragile site expression under conditions of folate deprivation was compared in the chromosomes from 5 Alzheimer's disease (AD) female patients, 5 healthy elderly females and 5 healthy young females. Although different fragile sites were observed in the three groups, nevertheless, more similarities were found between the AD patients and elderly normal donors. The only fragile site common to all groups was 3p14. This site was the most frequent in the young donors group. In both AD and elderly control groups we observed a higher frequency of fragility in 6p21, but not in the young controls. Other interesting fragility points observed in these two groups were: 6q21 and 14q24 (in the AD patients) and 9q13, 14q24 and 17q21 (in the healthy aged). 6p21 and 17q21 have been proposed as 'new' fragile sites. We confirm the existence of these fragile sites and comment that in these bands the genes MTBT2 and MTBT1, which are microtubule (beta) associated protein tau-like and tau 1, respectively, are mapped. The tau protein is a component of paired helical filaments which accumulate in degenerating neurons in the brain of patients with AD and with less intensity of normal elderly individuals.
 ...
PMID:Fragile sites, Alzheimer's disease, and aging. 140 93

The monoclonal antibodies TAU-1 and AT8 are directed at human microtubule-associated protein tau epitopes that contain a dephosphorylated and phosphorylated Ser202, respectively, while AT180 and AT270 are anti-tau monoclonals with epitopes that require phosphorylated Thr181 and Thr231, respectively. We used these antibodies to study the developmental profiles of tau proteins in rat cerebral cortex and chicken optic lobes. In tau extracts from perinatal rat cerebral cortex. AT8 recognized one major protein band of approximately 50 kDa that peaks on postnatal day 6 and declines rapidly to lower levels at day 12. At later stages, the AT8 epitope was expressed by several adult tau isoforms that were, however, stained only very faintly in highly enriched samples. Two additional tau epitopes recognized by AT180 and AT270 were found to be expressed by one or two protein bands up to about postnatal day 19 and then declined. Unlike the AT8 epitope, in the mature brain these epitopes were stained strongly in enriched samples, where they were expressed by a greater number of adult isoforms. Between embryonic day 19 and postnatal day 12, TAU-1 was found to recognize one major protein band of approximately 50 kDa which migrated slightly faster than the AT8-binding band. At postnatal day 19 and all older stages (including adult cortex), at least three additional TAU-1-binding isoforms with higher apparent molecular weights were present. Hence, the transition from one immature to several adult TAU-1-binding tau isoforms between postnatal day 12 and 19 in rat cerebral cortex coincides with the phase of rapid down-regulation of the AT8 epitope. As in the rat cerebrum, in chicken optic lobes there is a developmental decrease of AT8-binding proteins which is paralleled by striking changes in the electrophoretic pattern of tau isoforms recognized by TAU-1. In both rat cerebral cortex and chicken optic lobes, the period of maximal expression of AT8-binding tau is morphologically characterized by intense axonal growth and beginning synaptogenesis, whereas its subsequent rapid down-regulation and the appearance of novel TAU-1-binding isoforms correlates with synaptic maturation, the onset of spontaneous electrical activity and the beginning of myelination.
 ...
PMID:Developmental expression of tau proteins in the chicken and rat brain: rapid down-regulation of a paired helical filament epitope in the rat cerebral cortex coincides with the transition from immature to adult tau isoforms. 855 95

Different mutations in the microtubule-associated tau protein gene have recently been identified in several families with hereditary frontotemporal dementia and Parkinsonism (FTDP-17) linked to chromosome 17q21-22. Some families show neuronal and glial deposits containing hyperphosphorylated tau in several brain regions. We have investigated the presence of tau deposits by using a panel of anti-tau antibodies in three brains of a family with the P301L mutation (HFTD1) and in another family with the G272V mutation (HFTD2) of the tau gene. Numerous intracytoplasmic tau deposits in neurons, glial cells, and neurites were found in hippocampal formation, neocortex, and substantia nigra. These deposits in three patients from HFTD1 consisted of slender twisted filaments 15 nm wide with variable periodicity and a few straight filaments. Tau extracted from these filaments appeared as two major bands of 64 and 68 kd and a minor band of 72 kd that, after alkaline phosphatase treatment, proved to consist mainly of 4-repeat tau isoforms and one of the 3-repeat isoforms. In three patients from HFTD2 numerous Pick-like bodies were present. The conclusion is that the type and distribution of tau deposits in HFTD1 and HFTD2, the physical structure of filaments, and tau isoform composition in HFTD1 differ from Alzheimer's disease and an FTDP-17 family with a V337M mutation in the tau gene.
 ...
PMID:Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. 981 25

Conflicting evidence supports a role for tau as an essential neuronal cytoskeletal protein or as a redundant protein whose function can be fulfilled by other microtubule-associated proteins. To investigate the function of tau in axonogenesis, we created tau deficient mice by disrupting the TAU gene. The engineered mice do not express the tau protein, appear physically normal and are able to reproduce. In contrast to a previously reported tau knockout mouse, embryonic hippocampal cultures from tau deficient mice show a significant delay in maturation as measured by axonal and neuritic extensions. The classic technique of selectively enhancing axonal growth by growth on laminin substrates failed to restore normal neuronal maturation of tau knockout neurons. By mating human TAU-gene transgenic and tau knockout mice, we reconstituted tau-deficient neurons with human tau proteins and restored a normal pattern of axonal growth and neuronal maturation. The ability of human tau proteins to rescue tau-deficient mouse neurons confirms that tau expression affects the rate of neurite extension.
 ...
PMID:Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. 1122 61

Recently it was shown by several research groups that mutations in the gene encoding for the tau protein associated with microtubuli on chromosome 17 caused a distinct form of dementia named frontotemporal dementia and parkinsonism (FTDP-17). This disease includes familial asymmetrical frontal and, in the further course, frontotemporal dementia, parkinsonism, which is often initially sensitive to levodopa, signs of upper motor neuron degeneration, and, less commonly, amyotrophy. Tau is an intracellular protein of the cytoskeleton, which is responsible for the arrangement and stabilization of microtubuli. The discovery of mutations in the tau gene causing a distinct neurodegenerative disease in humans has firmly established the importance of the tau gene for neurodegenerative processes, not only in tauopathies but also in other degenerative disorders with tau pathology, such as corticobasal degeneration, supranuclear progressive paralysis, amyotropic lateral sclerosis, parkinsonism-dementia complex of Guam, and Alzheimer's disease. Our experience with patients suffering from PTDP-17 shows that its phenotype varies more than was described in the first consensus conferences. In the future, it will be important to designate the diagnostic gold standard not by clinical description, but etiologic classification.
 ...
PMID:[Tauopathies--a new class of neurodegenerative diseases]. 1125 58

During the postnatal development of cat visual cortex and corpus callosum the molecular composition of tau proteins varied with age. In both structures, they changed between postnatal days 19 and 39 from a set of two juvenile forms to a set of at least two adult variants with higher molecular weights. During the first postnatal week, tau proteins were detectable with TAU-1 antibody in axons of corpus callosum and visual cortex, and in some perikarya and dendrites in the visual cortex. At later ages, tau proteins were located exclusively within axons in all cortical layers and in the corpus callosum. Dephosphorylation of postnatal day 11 cortical tissue by alkaline phosphatase strongly increased tau protein immunoreactivity on Western blots and in numerous perikarya and dendrites in all cortical layers, in sections, suggesting that some tau forms had been unmasked. During postnatal development the intensity of this phosphate-dependent somatodendritic staining decreased, but remained in a few neurons in cortical layers II and III. On blots, the immunoreactivity of adult tau to TAU-1 was only marginally increased by dephosphorylation. Other tau antibodies (TAU-2, B19 and BR133) recognized two juvenile and two adult cat tau proteins on blots, and localized tau in axons or perikarya and dendrites in tissue untreated with alkaline phosphatase. Tau proteins in mature tissue were soluble and not associated with detergent-resistant structures. Furthermore, dephosphorylation by alkaline phosphatase resulted in the appearance of more tau proteins in soluble fractions. Therefore tau proteins seem to alter their degree of phosphorylation during development. This could affect microtubule stability as well as influence axonal and dendritic differentiation.
 ...
PMID:Differential Distribution of Tau Proteins in Developing Cat Cerebral Cortex and Corpus Callosum. 1210 43

Accumulation of abnormally modified tau protein (PHF-tau) is the principal intracellular lesion in a variety of neurodegenerative diseases, including Alzheimer's Disease (AD), but the cellular mechanisms underlying this accumulation are unknown. In this study, the cellular metabolism of PHF-tau purified from AD brain was investigated by microinjecting it into identified central neurons of the lamprey, a lower vertebrate. Dephosphorylation of 2 critical epitopes (the PHF-1 and TAU-1 sites), occurred within a few hours of PHF-tau microinjection, while proteolysis was complete by 2 days. These results constitute the first demonstration of the intracellular degradation of PHF-tau in an experimental in vivo system and suggest that the degradation of PHF-tau in situ is preceded by dephosphorylation. They also suggest that intracellular PHF-tau accumulation is primarily due to the failure of normal dephosphorylation and/or proteolytic mechanisms during neurofibrillary degenerative disease.
 ...
PMID:PHF-Tau from Alzheimer Brain is Rapidly Dephosphorylated and Degraded When Injected into Neurons in situ. 1221 14

Recent work on frontotemporal dementia (FTD) has revealed the existence of at least 3 genetically distinct groups of inherited FTD: FTDP-17, FTD and motor neuron disease linked to chromosome 9, and FTD linked to chromosome 3 (FTD-3). Tau, on chromosome 17, is the only gene where mutations have been identified and its involvement in FTD has been firmly established. The genes on chromosome 9 and chromosome 3 associated with familial forms of FTD remain to be identified. Abnormal aggregates of tau protein characterize the brain lesions of FTDP-17 patients and ubiquitin inclusions have been found in FTD with motor neuron disease linked to chromosome 9. In this study the frontal cortices of 3 FTD-3 patients from a unique Danish family were examined for characteristic neuropathological features. In these brains tau inclusions were present in neurons and some glial cells in the absence of beta-amyloid deposits. The presence of filamentous tau protein in the frontal cortex of these patients suggests a possible link between tau and the genetic defect present on chromosome 3 and associated with FTD-3, although the limited amount of tau deposits observed makes it difficult to define this as a tauopathy.
 ...
PMID:Tau protein in frontotemporal dementia linked to chromosome 3 (FTD-3). 1450 43

The relationship between senile plaques and neurofibrillary tangles, the main pathologic lesions of Alzheimer's disease, is not completely understood. We addressed this issue examining the type and amount of amyloid beta-protein (Abeta) associated with the soluble and insoluble tissue fractions in the frontal cortex of 8 cases with frontotemporal dementia with parkinsonism caused by mutations of the Tau gene (FTDP-17), in which the intracellular accumulation of polymerised tau is definitely the primary cause of neurodegeneration. As control, we examined 7 cases with frontotemporal dementia lacking distinctive histopathology (DLDH) as well as 8 pathologically normal subjects. In all cases the presence of Abeta deposits was ruled out using immunocytochemistry on sections adjacent to those used for biochemical analysis. ELISA analysis showed a 2.7 and 2.1 fold (p < 0.01) increase of soluble Abeta42 and Abeta40 in FTDP-17, compared to normal and DLDH brains, both of which had comparable levels of Abeta species. Furthermore, the immunoreactivity of the intracellular Abeta42 was significantly increased in cortical neurons of subjects affected with FTDP-17. The results demonstrate that the aggregation of tau protein produces an accumulation of Abeta, which, however, does not reach the critical concentration needed for Abetaplaques formation.
 ...
PMID:Soluble amyloid beta-protein is increased in frontotemporal dementia with tau gene mutations. 1500 27

Tau is a microtubule-associated protein mainly expressed in neurons of central nervous system, which is crucial in the maintenance of these cells. It has a central role in the polymerization and stabilization of microtubules and in the traffic of organelles along axons and dendrites. Aggregates of hyperphosphorylated forms of tau protein participate in the formation of neurofibrillary tangles, which characterize numerous neurodegenerative disorders named tauopathies. The analysis of tau gene and the study of familial cases of tauopathies have led to the discovery of tau gene mutations that cause inherited dementia designated as Frontotemporal dementia (FTD) with parkinsonism linked to chromosome 17 (FTDP-17). However, these familial cases remain rare compared to the sporadic tauopathies, the later involving both genetic and environmental etiologic factors. As tau pathology represents a primary pathogenic event in various neurodegenerative diseases, the hypothesis that tau genotype could influence the development of these diseases was tested by several groups. This review summarizes advances in the molecular genetics of the tau gene, as well as recent studies addressing the disease incidence of novel tau polymorphisms in different neurodegenerative diseases. Hopefully, the identification of several genetic defects of the tau gene will be helpful in improving our understanding of the role of tau protein in the pathogenesis of various neurodegenerative diseases.
 ...
PMID:Microtubule-associated protein tau gene: a risk factor in human neurodegenerative diseases. 1505 52


1 2 3 4 5 6 7 Next >>