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)

Ch4 neurons were studied morphometrically in three normal controls and three patients with Alzheimer's disease (AD). Two series of preparations stained with cresyl violet and with the indirect immunoperoxidase method using a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet were morphometrically analyzed. The cholinergic neurons were identified as positive reaction products of AChE in the perikarya. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer imaging system. Evaluation of these data provided a mean value of the cross-sectional neuronal area (CNA), number of neurons, standard deviation of the CNA and coefficient of variation of the cholinergic and noncholinergic neurons. The cholinergic neurons were decreased in number but showed hypertrophy in the early stage of AD, and they gradually became atrophic in the advanced stage. The noncholinergic neurons showed only atrophy without definite neuronal cell depletion. These findings indicate that cholinergic neurons have a plasticity and remodeling property against the AD process and suggest that hypertrophy of the cholinergic neurons in the Ch4 is the result of the effect of neurotrophic factors.
Mol Chem Neuropathol 1991 Dec
PMID:Morphometric study on the CH4 of the nucleus basalis of Meynert in Alzheimer's disease. 172 82

The most characteristic cellular change in Alzheimer's disease is the accumulation of aberrant filaments, the paired helical filaments (PHF), in the affected neurons. There is growing evidence from a number of laboratories that dementia correlates better with the accumulation of PHF than of the extracellular amyloid, the second major lesion of Alzheimer's disease. PHF are both morphologically and biochemically unlike any of the normal neurofibrils. The major polypeptides in isolated PHF are microtubule-associated protein tau. Tau in PHF is phosphorylated differently from tau in microtubules. This abnormal phosphorylation of tau in PHF occurs at several sites. The accumulation of abnormally phosphorylated tau in the affected neurons in Alzheimer's disease brain precedes both the formation and the ubiquitination of the neurofibrillary tangles. In Alzheimer's disease brain, tubulin is assembly competent, but the in vitro assembly of microtubules is not observed. In vitro, the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. The in vitro dephosphorylated PHF polypeptides stimulate microtubule assembly from bovine tubulin. It is hypothesized that a defect in the protein phosphorylation/dephosphorylation system is one of the earliest events in the cytoskeletal pathology in Alzheimer's disease. Production of nonfunctional tau by its phosphorylation and its polymerization into PHF most probably contributes to a microtubule assembly defect, and consequently, to a compromise in both axoplasmic flow and neuronal function. Index Entries: Alzheimer's disease; mechanisms of neuronal degeneration; neurofibrillary changes; paired helical filaments: biochemistry; microtubule-associated protein tau; abnormal phosphorylation; ubiquitination; microtubule assembly; axoplasmic flow; protein phosphorylation/dephosphorylation.
Mol Neurobiol 1991
PMID:Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease. 172 45

Concentrations of nervous tissue-related proteins, including S-100 proteins (alpha and beta), enolase isozymes (alpha and gamma), superoxide dismutase (SOD) isozymes (Cu/Zn SOD and Mn SOD), and GTP-binding proteins (alpha subunits of GO and Gi2) were determined in the four cerebrocortical regions (superior frontal gyrus of frontal lobe, parahippocampal gyrus of temporal lobe, superior parietal lobule of parietal lobe, and calcarine area of occipital lobe) of patients with Alzheimer's disease, and age-matched control and young control patients by means of enzyme immunoassay methods. Although the temporal cortex of some patients with Alzheimer's disease (4/7) showed apparently enhanced S-100 beta with decreased gamma-enolase, concentrations of neuronal (neuron-specific gamma-enolase and the alpha subunit of GO) and glial (S-100 beta, S-100 alpha, and alpha-enolase) marker proteins, and both SODs in each region were not significantly different between patients with Alzheimer's disease and the age-matched controls. Concentrations of Gi2 alpha also showed similar values in the cerebral cortices of young and aged controls and patients with Alzheimer's disease. However, when compared with young controls, S-100 beta in the four regions of patients with Alzheimer's disease and aged controls, and Cu/Zn SOD in frontal cortex of patients with Alzheimer's disease were significantly enhanced (P less than 0.01).
J Mol Neurosci 1991
PMID:Concentrations of several proteins characteristic of nervous tissue in cerebral cortex of patients with Alzheimer's disease. 181 96

Plasticity of the synaptic contact zone was previously observed following loss of synapses in the cerebral cortex of normal aging humans. The present study was undertaken to determine if there was quantitative evidence of synapse loss and synapse plasticity in the inferior temporal, superior parietal, parieto-occipital, and superior frontal cortical regions in Alzheimer's disease (AD), and how such changes related to the neurofibrillary tangles and amyloid plaques. The results showed that age at autopsy did not correlate with the numbers of synapses, plaques, or tangles. However, the numbers of synapses strongly reflected the pathology of AD; in all four brain regions, there were fewer synapses as the numbers of plaques and tangles increased. In the inferior temporal and superior parietal cortices, the loss of synapses was accompanied by an increase in the synaptic contact length. The results suggest that, in some cerebral cortical brain regions, synapses are capable of plasticity changes, even when the pathology of AD and loss of synapses are severe.
Mol Neurobiol 1991
PMID:Structural plasticity of synapses in Alzheimer's disease. 182 43

This paper describes an efficient technique for the production of metaphase spreads from single blastomeres biopsied from four-cell preimplantation mouse embryos. The karyotype obtained by chromosomal analysis of single biopsied cells is shown to be fully predictive of subsequent fetal karyotype. The data in this study also demonstrate that the entire process of embryo biopsy and karyotypic analysis of biopsied blastomeres does not adversely affect the ability of biopsied embryos to form fetuses after transfer into pseudopregnant recipients. This study has potential clinical relevance in that it demonstrates that chromosomally defective embryos can be accurately identified before implantation. In addition, the techniques developed in this study may facilitate more efficient procedures for the genesis of animal models for human disorders such as Down syndrome and Alzheimers disease.
Mol Reprod Dev 1991 May
PMID:Preimplantation embryo biopsy: detection of trisomy in a single cell biopsied from a four-cell mouse embryo. 182 51

L-Phosphoserine is a membrane metabolite that is elevated in Alzheimer's disease brain. This compound has close structural similarity to L-glutamate. Electrophysiological studies indicate that L-phosphoserine has an acute inhibitory effect, but a delayed excitatory action. A hypothesis is developed based on pharmacological and electrophysiological studies that suggest that the inhibition may be mediated through presynaptic inhibition of L-glutamate release or perhaps antagonism of postsynaptic kainic acid receptors. The mechanism of the delayed excitation may lie in the tendency of L-phosphoserine to mimic the action of L-2-amino-4-phosphonobutyric acid, a blocker of chloride- and calcium-sensitive L-glutamate transport. L-Phosphoserine has also been found to be a competitive antagonist at the N-methyl-D-aspartate recognition site and an antagonist of metabotropic receptor-mediated hydrolysis of inositol phospholipids. Because of these actions, there are several potentially important implications for the elevation of L-phosphoserine in Alzheimer's disease, including production memory impairment through presynaptic inhibition of L-glutamate release or blockade of postsynaptic N-methyl-D-aspartate receptors and/or blockade of certain L-glutamate transport sites resulting in increased L-glutamate levels in the synaptic cleft.
Mol Chem Neuropathol 1991 Aug
PMID:Possible roles of L-phosphoserine in the pathogenesis of Alzheimer's disease. 183 14

The technique of in situ hybridization with tritiated RNA probes was used to study the expression of the 68 kDa neurofilament (NF68) gene and the superoxide dismutase-1 (SOD-1) gene in the brains of Alzheimer's disease (AD) patients. Messenger RNA (mRNA) for these proteins was localized and quantified in single cells of formalin-fixed, paraffin-embedded sections of 4 pairs of AD and Huntington's disease (HD) brains from patients matched for age at death and autopsy interval. The cerebellar cortex and hippocampal CA1 and CA2 regions were compared in these two groups of subjects, since in AD the CA2 region of the hippocampus and the cerebellum have been found to be relatively unaffected by the Alzheimer process in comparison to the hippocampal CA1 region. The amount of NF68 mRNA was reduced by approximately 50% in pyramidal cells of both the CA1 and CA2 of AD hippocampus (P less than 0.001), and by 15% in the Purkinje cells of AD cerebellum (P less than 0.05) relative to that of the HD individuals. SOD-1 mRNA was reduced by about 22% in the CA1 of AD brains (P less than 0.001) with no corresponding reduction in the CA2, and by only 5% in the AD cerebellum (P greater than 0.5). The paired design of the study suggests that these results are not simply attributable to the effects of autopsy interval or the agonal process in each patient's death.
Brain Res Mol Brain Res 1991 Jan
PMID:Localization and quantitation of 68 kDa neurofilament and superoxide dismutase-1 mRNA in Alzheimer brains. 185 65

Homogenates prepared from the temporal cortex and hippocampus of individuals who had histopathologically confirmed Alzheimer's disease exhibited reduced in vitro cyclic AMP-dependent phosphorylation of synapsin I, neuronal phosphoprotein. One specific phosphorylation site (site 1) was affected while two other sites, which are phosphorylated by calcium/calmodulin kinase II, exhibited no such differences. Other phosphoproteins such as pyruvate dehydrogenase, did not show these differences. The reductions were not observed in either cerebellum or thalamus of Alzheimer's disease brain. Analysis by immunoblots indicated that the reductions were not caused by a decrease in absolute amounts of the protein. The reduced AD synapsin I phosphorylation was not overcome by the addition of purified cyclic AMP-dependent protein kinase. No differences were detected in total cyclic AMP-dependent protein kinase activity between the control and Alzheimer samples. However, dephosphorylation of the synapsin I prior to the in vitro phosphorylation reversed the differences observed between the control and AD homogenates. Thus, the reduced in vitro phosphorylation of the synapsin I in the Alzheimer homogenate reflects a reduced phosphorylatability of the protein due to either an increased phosphate content or some other alteration of the phosphorylation site.
Brain Res Mol Brain Res 1991 Jan
PMID:Reduced in vitro phosphorylation of synapsin I (site 1) in Alzheimer's disease postmortem tissues. 185 67

Transcriptional regulation of the gene encoding the amyloid precursor protein (APP) may play an important role in the formation of the amyloid depositions observed in Alzheimer disease and Down syndrome patients. To determine the promoter sequence requirements for the expression of the APP gene, we constructed plasmids containing different parts of the APP gene promoter fused to the bacterial chloramphenicol acetyl transferase (CAT) gene. Transfection of these constructs into Hela and PC12 cells revealed the presence of two blocks of regulatory sequences in the APP promoter. One block extending from about -600 to -460 bp acts as a positive regulator as its removal results in a substantial decrease in promoter activity. A second block of sequences extending from -450 to -150 bp acts like a negative regulator. We have also observed that a 38 mer synthetic oligonucleotide encompassing the region -489 to -452 of the APP promoter stimulated the activity of the heterologous TK promoter, suggesting that this region may be part of an enhancer-like element. In addition, our results suggest that the effects of various APP promoter domains on its activity may be cell specific.
Brain Res Mol Brain Res 1991 Feb
PMID:The promoter activity of the gene encoding Alzheimer beta-amyloid precursor protein (APP) is regulated by two blocks of upstream sequences. 185 27

An S1 nuclease protection assay was designed to study the splicing pattern of the alternatively spliced beta A4 amyloid gene (APP gene) of Alzheimer's disease (AD). We determined the splicing pattern of the APP gene in fetal, adult, aged adult and AD human cortex. The results suggest that alternative splicing of the APP gene in AD is not significantly different from age-matched controls, but distinct from the developing fetal brain.
Brain Res Mol Brain Res 1991 Feb
PMID:Alternative splicing of the beta A4 amyloid gene of Alzheimer's disease in cortex of control and Alzheimer's disease patients. 185 28


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