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)

1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.
Cell Mol Neurobiol 1992 Dec
PMID:Monoamine neurotransmitters and their metabolites in brain regions in Alzheimer's disease: a postmortem study. 128 63

Following the identification of mutations in the beta-amyloid precursor protein (APP) gene in familial, early onset Alzheimer's disease (AD), we have developed a screening protocol using single strand conformation analysis (SSCA) to screen exon 17 for the known mutations within APP. In addition, we used this protocol to screen the other seventeen exons of APP and a three hundred and thirty base pair regulatory region of the promoter for new mutations in 9 families with early onset AD. Exons 16 and 17, which encode the deposited beta-amyloid peptide, were screened in a further 10 families. Our screening procedure identifies all the reported mutations within APP. While we have identified a further family with APP717 Val-->Ile, we did not find any previously undescribed mutations. Screening of other exons of APP in 2 families in which we have previously reported mutations at APP717, failed to reveal other sequence abnormalities supporting the hypothesis that the mutations at APP717 cause the disease in these families. These data suggest that mutations in APP are a rare cause of familial early onset AD (3/21 families tested) and that within APP most, possibly all, mutations which cause AD are in exon 17.
Hum Mol Genet 1992 Jun
PMID:Screening for mutations in the open reading frame and promoter of the beta-amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile. 130 72

Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression. Calcium/calmodulin dependent protein kinase II (CaM kinase II) has been shown to phosphorylate tau in vitro in such a way to decrease its electrophoretic mobility. A68, apparently a modified form of tau in AD brain, also shows abnormal phosphorylation and slower mobility than tau. To further examine the role of CaM kinase II in AD, in situ hybridization studies were performed on tissues from rat, monkey and human to examine and compare the patterns of CaM kinase II mRNA expression in different brain regions. The most notable differences among the three species were observed in dendrites in layer I of isocortex, in the molecular layer of the dentate gyrus and stratum radiatum and stratum lacunosum-moleculare in hippocampus, where hybridization was detected in rat, but not in monkey or human brain. In addition, comparisons between tau and CaM kinase II mRNA expression were made in tissue from normal aged adults and AD patients, especially in areas prone to NFT formation. CaM kinase II and tau mRNAs were co-expressed in many neuronal populations, both those which are prone to NFT formation as well as those which are rarely affected by AD changes. No major differences in the relative abundance of either CaM kinase II or tau mRNA within particular neuronal populations was noted between normal aged and AD brain. Diminished hybridization was associated with serve neuronal pathology and cell loss.
Brain Res Mol Brain Res 1992 Jan
PMID:In situ hybridization of calcium/calmodulin dependent protein kinase II and tau mRNAs; species differences and relative preservation in Alzheimer's disease. 131 9

Receptors for vitamin D hormone (VDR) and the calcium binding protein, calbindin-28k, have been localized in many tissues, including brain. In brain, VDR and calbindin-28k were reported to colocalize in hippocampal CA1 cells. We have shown that mRNA pool size for calbindin-28k was reduced, on average, by 35% in Alzheimer hippocampal CA1 cells, as compared to Huntington control (manuscript in preparation). In the present study, in situ hybridization with tritiated antisense RNA probes was used to examine VDR expression in paired Alzheimer and Huntington brain tissue. Message levels for VDR were reduced, on average, by 34% and 31%, respectively, in Alzheimer hippocampal CA1 and CA2 pyramidal cells, as compared to Huntington control. However, VDR message levels were not significantly different from control in Alzheimer temporal cortex or cerebellum. There was no correlation between VDR message levels and brain weight, autopsy interval, patient age or the extent of neurofibrillary degeneration. Instead, VDR mRNA pool size in hippocampal CA1 cells correlated significantly with calbindin-28k message levels (r = 0.52, P less than 0.001). Decreased message levels for VDR and calbindin-28k in these cells were due to an increased percentage of cells expressing lower message levels for these proteins. These results show that in Alzheimer hippocampal CA1 cells, VDR mRNA pool size is downregulated and that this downregulation may play a role in the reduction of calbindin-28k expression.
Brain Res Mol Brain Res 1992 Apr
PMID:Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels. 131 96

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.
J Mol Neurosci 1992
PMID:Continuous culture of neuronal cells from adult human olfactory epithelium. 132 Sep 21

Many investigators have reported the presence of complement proteins in Alzheimer disease (AD) brains, but their origin is uncertain. We report the expression of complement genes C1q, C3 and C4 in RNA extracted from temporal cortex samples of post-mortem human brain. The transcripts for C3 and C4 were detected by Northern hybridization analysis, and the mRNAs for C1q, C3 and C4 were detected by polymerase chain reaction (PCR) amplification of brain derived complementary DNA (cDNA). The relative abundances of mRNAs for C3 and C4 were compared between samples of temporal cortex from neurologically normal and Alzheimer disease (AD) cases, using a semiquantitative PCR assay. There was a 3.01 fold mean increase in expression of C3 and a 3.27-fold mean increase in expression of C4 in AD samples compared to control cases. These results indicate that localized synthesis of some of the major complement components can occur in human brain. The factors causing activation of complement in AD still remain undetermined.
Brain Res Mol Brain Res 1992 Jun
PMID:Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. 132 7

In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP770, APP751 and APP695. The former two types harbor, but the latter one lacks a domain of Kunitz-type serine protease inhibitor (KPI). We studied, by using the RNase protection technique, the expression of APP mRNAs in brains of Alzheimer's disease (AD) and other neurological disorders with special reference to aging. We found that the ratio of (APP770 mRNA+APP751 mRNA)/APP695 mRNA in the frontal cortex increased approximately 1.5-fold in AD compared with other neurodegenerative or cerebrovascular disorders. The ratio in other neurological disorders did not change significantly from control even in their affected brain regions. On the other hand, we found a positive correlation between the ratio and age; the ratio (y) increased gradually with the advance of age (x) as expressed by y = 0.005x + 0.014 (r = 0.372) for the AD group, and y = 0.004x -0.037 (r = 0.486) for the non-AD group. These correlations indicate that the AD brain reached the same ratio of KPI-harboring to lacking APP mRNAs a few decades earlier than the non-AD brain in senescence. This finding of AD-specific and age-related change led us to the idea that a relative increase in KPI-harboring APPs over a KPI-lacking APP may perturb normal degradation of APPs, thereby leading to deposition of beta A4 protein as amyloid.
Brain Res Mol Brain Res 1992 Oct
PMID:Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders. 133 85

Elongation factor 2 (EF-2) is a phosphoprotein that mediates the translocation step of elongation during protein synthesis. We investigated its phosphorylation to characterize translational regulation of gene expression in Alzheimer's disease. EF-2 was identified on two-dimensional (2D) gels of brain homogenates by analyzing immunoblots with EF-2-specific antibody (M(r) 96,000; pI 6.8). Four distinct charge variant isoforms were observed. We identified the two most acidic isoforms as being the phosphorylated forms by incorporation of radiolabeled phosphate. The phosphorylation of EF-2 in control and Alzheimer's disease (AD) brain was directly measured as the distribution of the four polypeptides on silver stained 2D gels. The ratio of the phosphorylated forms to unphosphorylated forms was elevated 45% in AD homogenates compared to controls (1.07 +/- 0.18; n = 9 vs 0.73 +/- 0.20; n = 6; P less than 0.004) which indicated an increased phosphorylation of AD EF-2. The phosphorylation exhibited specificity to the disease in that it was observed in affected areas (cortex and hippocampus) but not in an unaffected area (thalamus) of the same brains. Because phosphorylation of EF-2 inhibits protein synthesis, the observed AD-associated phosphorylation of EF-2 is consistent with the reduced in vitro activity of polysomes isolated from AD tissues that we have previously reported.
Brain Res Mol Brain Res 1992 Oct
PMID:Increased phosphorylation of elongation factor 2 in Alzheimer's disease. 133 87

Pure domoic acid is required for use in research to investigate the biological effects of this new shellfish toxin. It may also prove to be a useful tool in studies exploring the basis of Alzheimer's disease. In this paper we describe a procedure which is effective in obtaining adequate quantities of pure domoic acid from blue mussel (Mytilus edulis). The procedure involves tissue homogenization, treatment of homogenate with chloroform and methanol, and separation of different phases with the addition of water. The aqueous-methanolic phase (upper layer) contains water soluble components including domoic acid, the chloroform phase (lower layer) contains lipoid moieties, and the interphase contains denatured proteins. The aqueous phase containing domoic acid was removed, rotory evaporated to get rid of methanol, followed by ultrafiltration to remove high molecular weight contaminants. The filtrate was lyophilized, resuspended in 1 N HCl, centrifuged and the resulting clear solution subjected to column chromatography on C18 reversed phase silica gel. Fractions containing domoic acid were pooled, and lyophilized. A brownish dry powder contained pure domoic acid with 60-65% yield from the original tissue homogenate. Another 10-15% of domoic acid was mixed with its isomer, and can be further resolved to obtain an overall recovery of 75-80% of the starting material.
Mol Cell Biochem 1992 Oct 07
PMID:A procedure for large-scale purification of domoic acid from toxic blue mussels (Mytilus edulis) 133 39

The origin of beta-amyloid deposited in senile plaques in Alzheimer's disease (AD) is not known. We compared the expression of protein precursor of beta-amyloid (APP) in the cell types involved in plaque formation. The levels of APP mRNA were determined in primary rat neurons and glial cells in culture, human endothelial cells and in a murine brain-derived endothelial cell line. Northern blot analysis was performed using an APP cDNA probe to detect the general APP sequence and an oligonucleotide (40 mer) complementary to the sequence of the Kunitz protease inhibitor (APP-KPI). The APP mRNA transcripts were abundant in all three cell types. The highest level of APP, normalized to beta-actin mRNA content, was expressed in neurons, followed by glial cells, where the APP expression was similar (94%) while in endothelial cells was lower (53%). The proportion between APP-KPI mRNA and total APP mRNA was high in endothelial, intermediate in glial and low in neuronal cells. We compared the effects of exposure to interleukin-1 (IL-1), a cytokine involved in several biological processes and elevated in AD, on APP mRNA expression in neuronal, glial and endothelial cells. In human endothelial and in brain-derived murine endothelial cells we observed a similar increase (50%) of total APP mRNA or APP-KPI mRNA after treatment with human recombinant IL-1 beta. In neuronal cells, IL-1 (200 ng/ml) substantially increased APP mRNA (175%), detected with both probes. In glial cells, the expression of APP mRNA did not appear to be altered by IL-1 (50-400 ng/ml). The results suggest a role of IL-1 in the neuronal mechanisms related to beta-amyloid protein deposition in AD.
Brain Res Mol Brain Res 1992 Nov
PMID:Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. 133 90


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