Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many of the human neurodegenerative conditions involve a reorganization of the neuronal cytoskeleton. The way in which the cytoskeleton is reorganized may provide a clue to the nature of the insult causing the neurodegeneration. The most common of these conditions is Alzheimer's disease, in which microtubules are lost from neurites that fill up with filamentous structures. One component of the filamentous structures is the microtubule-associated protein (MAP), tau. The tau protein is the product of a single gene expressed predominantly in neurons. The tau gene undergoes complex alternative splicing that is regulated both by development, and by the particular neuronal cell population in which it is expressed. Tau protein can be further modified, following its translation by phosphorylation at several sites. Much of the recent interest in the transition of tau to an abnormal state within a tangle-bearing neuron has focused on phosphorylation. A group of proteins that migrate slightly more slowly than tau, designated PHF-tau, are found in regions of the Alzheimer brain rich in dystrophic neurites, are hyperphosphorylated, fail to bind to microtubules, have distinct solubility properties, and can be derived from fractions of paired helical filaments (PHF).
Mol Neurobiol
PMID:Tau protein and neurodegeneration. 213 93

Quinolinic acid, an excitotoxic agent, was applied unilaterally to the nucleus basalis magnocellularis of the rat forebrain, which resulted in neuronal destructions and consequently, loss of cholinergic projections to the cortex. The effects on ganglioside metabolism in brain cortical matter were studied. Total ganglioside contents in lesioned brains (n = 8) were found to be significantly decreased (range, 20-60%) but changes in brain ganglioside patterns on thin layer chromatograms were not apparent. On the other hand, in vivo incorporation of N-acetyl-D-[U-14C]mannosamine into brain gangliosides ranged from 19 to 36% (mean, 26%) of radiolabel in controls, and 5 to 21% (mean, 13%), a significant reduction in lesioned brains. Labeling of brain glycoproteins or of nonganglioside lipids was not affected. Since central cholinergic hypofunctions are also important neurochemical characteristics of Alzheimer's disease, abnormal ganglioside metabolism found in the lesioned rats may be of significance in the human disorder, where reduced brain ganglioside contents have also been reported.
Mol Chem Neuropathol 1990 Dec
PMID:In vivo incorporation of N-acetyl-D-[U-14C]mannosamine into brain gangliosides of rats with quinolinic acid-induced lesions of the forebrain nucleus basalis magnocellularis. 215 95

Light micrococcal nuclease digestion was used to examine DNA associated with nucleosome populations isolated from Alzheimer's disease (AD) affected superior temporal lobe neocortical nuclei. 46.1% of the immediate 5' upstream DNA sequence of the single copy neurofilament light chain (NF-L) gene was found to be associated with a mononucleosome fraction in control neocortices. This fraction was reduced to 7.4% in age-matched AD-affected neocortex. No differences in accessibility to the nuclease probe was found between AD-affected and control temporal grey matter nuclei for the human prion HuPrP gene or for the NF-L gene in nuclei isolated from the primary visual cortex or the cerebellum. An AvaI restriction endonuclease site, located 124 base pairs upstream from the TATAA box in the NF-L leader sequence, was also found to be occluded in AD-affected nuclei. From this and previous data we conclude that within the AD-affected nucleus, focused changes in neuronal chromatin conformation occur. Increases in the packing density of chromatin may reduce transcription and alter the ability of neurons to generate sufficient levels of gene products to maintain normal neocortical function.
Brain Res Mol Brain Res 1990 Apr
PMID:Chromatin structure and gene expression in Alzheimer's disease. 215 82

The recovery of RNA from postmortem (PM) brain tissues was quantified by molecular hybridization. RNA degradation rates postmortem were faster in mice with herpes encephalitis than with uninfected mice, but clear ribosomal peaks could be seen up to 72 hr after death. In a comparison between frontal cortex samples from neurologically normal and Alzheimer's disease cases a reduction in ribosomal, poly A, preproenkephalin, and preprosomatostatin RNA levels was observed in the Alzheimer's disease group. This general reduction may be influenced by the cause of death as well as the pathology.
Exp Mol Pathol 1986 Feb
PMID:Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization. 241 56

Recent findings of the protease inhibitor domain in amyloid precursor protein of Alzheimer's disease (APPI) raised a novel hypothesis on the mechanism of amyloid deposition in the brain. APPI has significant amino acid sequence homology with Kunitz-type basic trypsin inhibitor super-family proteins, and the gene expression product showed real inhibitory activity. Since the three-dimensional model of APPI would help in understanding biological phenomena in molecular detail, we constructed an atomic model of APPI based on the structure of bovine pancreatic trypsin inhibitor (BPTI). The substitution of BPTI side chains by best-fitting corresponding amino acid structures was followed by the removal of van der Waals overlappings by molecular mechanics energy minimization with the AMBER force field, to give the feasible model of APPI. We also built serine protease models based on the structure of trypsin and investigated the target enzyme specificity of the inhibitory activity by the active-site mapping method. The models can explain the relative enzyme spectra of APPI and BPTI.
J Mol Graph 1989 Dec
PMID:Structure prediction of protease inhibitor region in amyloid precursor protein of Alzheimer's disease. 248 10

Aging of the brain is characterized, in part, by the appearance of protein anomalies. The proteins deposited within the nervous system structures are hardly soluble. This physiological phenomenon turns out to be pathological, quantitatively at least, and perhaps even qualitatively, in dementia of the Alzheimer's type (DAT). One might wonder whether the brain protein anomalies are related to a general process and, thus, could generate anomalies of the serum proteins. Therefore, we examined, with two-dimensional electrophoresis (2DE), 120 serum samples collected from different neurological patients and 24 serum samples from a control group, and we reached the following conclusion: a protein spot, normally not found and named 10M, corresponding to a molecular weight of 30 kDa with an isoelectric point of +/- 8, is seen in 31% of the patients affected with a neurological disease and in 90% of patients affected with DAT. The frequency of the appearance of this spot, seen after 2DE, increases with age. We wonder whether this protein is playing a role in the formation of the neuropathological lesions observed in DAT.
Mol Chem Neuropathol 1989 Dec
PMID:A serum protein involved in aging? 248 32

Tau proteins consist of a family of proteins, heterogeneous in size, which associate with microtubules in vivo and are induced during neurite outgrowth. In humans, tau is one of the major components of the pathognomonic neurofibrillary tangles in Alzheimer's disease brain. Screening of a cDNA library prepared from bovine brain led to the isolation of several cDNA clones encoding tau proteins with different N termini and differing by insertions or deletions, suggesting differential splicing of the tau transcripts. One of the N-terminal domains and the repeated C-terminal domain of the encoded tau proteins are recognized by polyclonal antibodies to bovine tau. The bovine tau proteins are highly homologous to murine and human tau, especially within the repeated C-terminal domain. Compared with murine and human tau, bovine tau contains the insertion of three longer segments, one of which is an additional characteristic repeat. Portions of tau proteins generated by in vitro translation were used to show that these repeats represent tubulin-binding domains, two of which are sufficient to bind to microtubules assembled from purified tubulin in the presence of taxol.
Mol Cell Biol 1989 Apr
PMID:Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. 249 49

Tau, a major class of microtubule-associated proteins, consists of a family of proteins that are heterogeneous in molecular weight. The presence of internal deletions in previously described cDNA clones for murine and bovine tau suggested that alternative splicing of transcripts could account for the protein size heterogeneity. Analysis of the exon-intron structure of the bovine tau gene provided sequence information necessary to detect new variants of tau transcripts by in vitro amplification techniques. The variant transcripts found corresponded to mRNA species missing one or more exons, which suggested that by skipping various exons during mRNA splicing, a family of proteins is generated. Four major tau protein isoforms isolated from bovine brain were identified by comparison with translation products of cDNA constructs and the use of antisera raised against synthetic peptides. These studies provide reagents and a basis for analyzing potentially altered forms of tau proteins in brains of patients with Alzheimer's disease.
Mol Cell Biol 1989 Apr
PMID:Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family. 249 50

Two classes of amyloid beta-protein precursors which differ by the presence of a serine protease inhibitor domain have been described. We have used synthetic oligonucleotide probes to investigate the tissue distribution and cellular localization of mRNAs encoding the two classes of amyloid beta-protein precursors. RNA blot analysis showed that transcripts encoding the protease inhibitor sequence are ubiquitously expressed in peripheral and central tissues. By contrast, transcripts lacking the protease inhibitor domain were only found in the central nervous system. By in situ hybridization on cerebral cortex and hippocampal formation both types of transcripts were present exclusively in nerve cells and they appeared to be produced by the same cells. A reduction in the transcript lacking the protease inhibitor domain was observed in frontal cortex from Alzheimer's disease patients. The present results indicate that there exists no correlation between the distribution of amyloid amyloid beta-protein precursor mRNAs and the tissue and cellular pathology of Alzheimer's disease; they also suggest that an overproduction of amyloid beta-protein precursor mRNA is unlikely to be responsible for amyloid beta-protein deposition in Alzheimer's disease.
Brain Res Mol Brain Res 1989 Nov
PMID:Expression and cellular localization of amyloid beta-protein precursor transcripts in normal human brain and in Alzheimer's disease. 251 8

Quantitative analysis of total gangliosides and of ganglioside composition by HPTLC has been carried out on the gray matter of frontal cerebral cortex of six brains from Down's syndrome (DS) adults, six age-matched controls, six Alzheimer's disease (AD) adults, and six controls matched for age with the AD brains, as well as on three DS and six control cerebellum specimens. In addition, the analyses were carried out on specimens of corpus callosum of five adult DS and five control brains. No abnormalities were found in the gangliosides of DS corpus callosum. In DS frontal cortex, the concentration of total gangliosides was reduced, and there was a decrease in the fraction of GT1b and GD1b, and an increase in those of GT1a, GD3, GM1 and GM2; the ratio of total b-series to a-series gangliosides was decreased. Very similar abnormalities were found in the gangliosides of DS cerebellum. In AD frontal cortex, by contrast, the total gangliosides and their composition were normal by comparison with age-matched controls, with the minor exception of reductions in the fractions of GQ1b and GT1L. It is concluded that abnormalities in gangliosides exist in the brain in DS that are unrelated to AD-type pathology and may reflect developmental disturbances.
Mol Chem Neuropathol 1989 Dec
PMID:Gangliosides in the brain in adult Down's syndrome and Alzheimer's disease. 253 85


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