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)

The GTP binding protein, Gs, activates adenyl cyclase in direct response to stimulation of several neurotransmitter receptors. In situ hybridization histochemistry (ISHH) with a 35S-labelled oligonucleotide has been used to detect the mRNA encoding the alpha subunit of Gs (Gs alpha) in human hippocampus, temporal and visual cortices and cerebellum, and its level has been compared between Alzheimer's disease (AD) and control brains. A marked regional increase was found in the hippocampus of AD cases. Analysis of levels of Gs alpha mRNA in individual constituent pyramidal cells confirmed this increase (3 to 4-fold in densitometric units) in hippocampal fields CA1, CA3 and CA4, as well as in temporal cortex. Levels of Gs alpha mRNA were also determined relative to total poly(A)+ mRNA in the same cell populations in each case. Gene-specific elevation of Gs alpha mRNA was thereby confirmed in hippocampal fields, and also in temporal cortex. No changes were seen in visual cortex. The increase in Gs alpha mRNA may represent a response by AD neurons in affected areas to receptor alterations, or to an abnormality in receptor-G protein coupling. Alternatively, altered G protein gene expression might be a pathogenic event underlying changes in linked receptor populations.
Brain Res Mol Brain Res 1991 Apr
PMID:Alzheimer's disease: specific increases in a G protein subunit (Gs alpha) mRNA in hippocampal and cortical neurons. 164 85

The nucleus basalis of Meynert was lesioned by infusion of N-methyl-D-aspartate (NMDA) unilaterally in adult rat brain. Seven days post lesion we observed that polysomes isolated from the cerebral cortex affected by the lesion synthesized 2.6-fold greater amounts of the Alzheimer amyloid precursor protein (AAPP) compared to the nonlesioned side of the same rat brain. This increase exhibited specificity to AAPP in that overall protein synthesis was not altered by the lesion. The increase of AAPP did not alter the ratio of AAPP isotypes in rat brain (in which AAPP 695, which is lacking the protease inhibitor insert remains the predominant form). The increased synthesis did not result in the apparent accumulation of mature AAPP. These results indicate that a cholinergic lesion which models many of the neurochemical changes observed in Alzheimer's disease induces the expression of AAPP in a major projection region, the cerebral cortex.
Brain Res Mol Brain Res 1991 May
PMID:Increased biosynthesis of Alzheimer amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert. 164 69

The beta-amyloid precursor protein (APP) is involved in the degenerative and regenerative neural changes associated with aging and Alzheimer's disease. We studied the regulation of APP gene expression in a paradigm of degeneration and regeneration, the axotomized rat sciatic system. The sciatic nerves of rats were crushed and at intervals between 4 and 60 days, the affected dorsal root ganglia and spinal cord segments were processed for Northern analysis and in situ hybridization to evaluate various APP mRNA species. After nerve crush, dorsal root ganglia APP mRNA levels are increased for both APP695 (695 amino acids) and APPKPI (Kunitz protease inhibitor). Following reinnervation, APP695 returns to baseline but APPKPI remains elevated. In spinal cord there is a decrease of APP695, which returns to baseline following reinnervation. If regeneration is prevented, the initial phase of post-axotomy response for all APP forms persists for at least 60 days in both dorsal root ganglia and spinal cord. In situ hybridization confirms that the changes are referable to neurons. These findings indicate that neuron-target interactions are important in APP gene regulation; that the APP695 and APPKPI transcripts are differentially regulated following neuronal injury; and that different neuronal populations regulate APP expression in a cell-type specific manner.
Brain Res Mol Brain Res 1991 Jul
PMID:Beta-amyloid precursor protein gene is differentially expressed in axotomized sensory and motor systems. 165 58

The amyloid beta protein (ABP) has been shown to interact with the substance P (SP) receptor in a cell culture model that may mimic the pathogenesis of Alzheimer's disease. In the present study, however, 4 fragments of ABP (beta 1-42, beta 1-16, beta 17-28, and beta 25-35) failed to interact with SP-induced Ca2+ mobilization in SP receptor-expressing cultured cells. Therefore, the action of these ABP-related peptides in our cultured cells is unrelated to the SP receptor.
Brain Res Mol Brain Res 1991 Sep
PMID:Amyloid beta protein substituent peptides do not interact with the substance P receptor expressed in cultured cells. 166 16

Postmortem cortical tissues from Alzheimer's disease cases were found to contain significantly higher levels of the heat shock proteins hsp 72 and hsp 73 than control cortical tissues. This elevation was associated with the disease pathology in that it was not observed in Alzheimer's disease cerebella and was not correlated with perimortem characteristics such as age or cause of death of the patient or postmortem interval of the brain tissue. Examination of polysome translation products on two dimensional gels and by immunoprecipitation indicated that the syntheses of hsp 72/73 were increased in Alzheimer's disease tissues. In addition, immunoprecipitation of newly synthesized hsp 72 showed that numerous other nascent polypeptides were co-precipitated, which indicates an irreversible cotranslational association with the hsp 72. These results indicate that induction of specific heat shock proteins is associated with Alzheimer's disease and that cotranslational processes are affected by this induction.
Brain Res Mol Brain Res 1991 Oct
PMID:Increased synthesis and accumulation of heat shock 70 proteins in Alzheimer's disease. 166 22

A 35S-labelled synthetic oligonucleotide directed against part of the mRNA coding for the M1 subtype muscarinic receptor was used for in situ hybridization histochemistry in sections of human temporal cortex. M1 receptor mRNA was found in cell populations throughout the grey matter, especially in pyramidal cells. Quantitative densitometric analysis of autoradiograms was used to compare levels of this mRNA between Alzheimer's disease and controls. A significant (2.7-fold) increase in hybridization signal was found in Alzheimer's disease cases, both in absolute terms and relative to total polyadenylated mRNA as determined by hybridization with an oligodeoxythymidine probe. Elevated levels of muscarinic receptor mRNA may reflect up-regulation of transcription of this gene in response to the cholinergic deficits occurring in the disease.
Brain Res Mol Brain Res 1991 Jan
PMID:Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry. 167 14

In situ hybridization histochemistry has been used to study the amount of M1 muscarinic receptor mRNA in temporal cortex from subjects with Alzheimer's disease and other neurodegenerative disorders, where the duration of terminal coma was known. Total polyadenylated mRNA and glutamate decarboxylase activity were also measured. Both muscarinic receptor mRNA and enzyme activity showed a significant decline with increasing duration of terminal coma, but were not related to diagnosis. Polyadenylated mRNA signal did not show an association with coma. These data indicate the need to consider the nature of the terminal illness in post mortem studies of mRNA as well as for neurochemical research.
Brain Res Mol Brain Res 1991 Jan
PMID:Terminal coma affects messenger RNA detection in post mortem human temporal cortex. 167 15

Complement proteins of the classical pathway can be immunohistochemically identified in cerebral amyloid plaques in Alzheimer's disease. Microglial cells in and around amyloid plaques express class II major histocompatibility (MHC) antigens and complement receptors CR3 and CR4. Negative immunostaining for immunoglobulins and for T-cell subsets in the brain parenchyma demonstrates a lack of evidence for the involvement of specific immune responses (such as an immune complex-mediated complement activation or a cell-mediated immune response) in cerebral amyloid deposits in Alzheimer's disease. Cerebral amyloid plaques in scrapie-affected mice (slow-virus induced encephalopathy) do not contain complement factors C1q and C3c and are not clustered with microglial cells expressing MHC class II molecules or complement receptor CR3. The data presented suggest the induction of a reactive inflammatory process by beta/A4 amyloid in the human brain, but not by scrapie-induced PrP amyloid in mice. Our findings do not support the hypothesis that the immune system is involved in the generation of amyloid plaques in Alzheimer's disease.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Cerebral amyloid plaques in Alzheimer's disease but not in scrapie-affected mice are closely associated with a local inflammatory process. 168 40

The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel recording techniques. THA produced a concentration-dependent block of NMDA-evoked inward current responses (IC50, 190 microM at -60 mV), without affecting responses to quisqualate or kainate. THA block of NMDA responses was voltage dependent and was nearly completely relieved at positive holding potentials. Analysis of the voltage dependency indicated that the THA binding site senses 56% of the transmembrane electrostatic field. In single-channel recordings from outside-out membrane patches, THA appeared to reduce the frequency and duration of NMDA-evoked single-channel currents, without affecting the single-channel amplitude. The effects of THA on NMDA responses occur at concentrations 1-2 orders of magnitude greater than the therapeutic serum concentrations and, therefore, blockade of NMDA receptor-mediated responses is unlikely to contribute to the putative therapeutic action of THA. However, because NMDA receptors may play a critical role in cognitive and memory function, THA has the potential to produce undesirable central nervous system side effects at high doses.
Mol Pharmacol 1991 May
PMID:Tetrahydroaminoacridine block of N-methyl-D-aspartate-activated cation channels in cultured hippocampal neurons. 170 20

Complementary oligonucleotide probes specific for the human pro-opiomelanocortin (POMC) mRNA were used to analyze the expression of POMC gene in 56 human postmortem pituitaries by in situ hybridization histochemistry. POMC transcripts were visualized by autoradiography in anterior lobe of the pituitary where their distribution was in a 'patchy-like' pattern. No hybridization could be observed in the posterior lobe of the pituitary. We examined pituitaries from several controls and from patients dying with schizophrenia, Parkinson's disease. Alzheimer's disease, Wernicke's encephalopathy and depressive illness. Computer-assisted microdensitometric semiquantification of POMC mRNA using a complementary oligonucleotide as hybridization standard, revealed no statistically significant effect of postmortem delay (between 2.5 and 66 h), of gender, age (between 22 and 103) or cause of death in 56 human pituitary glands. A large variation in POMC levels was already observed among all 30 control cases. The levels of POMC mRNA observed in pituitaries from different pathologies did not show a significant variation when compared with control cases.
Brain Res Mol Brain Res 1991 May
PMID:Study of pro-opiomelanocortin mRNA expression in human postmortem pituitaries. 171 87


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