Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid beta protein precursor (APP). This 653-amino acid protein, which we have termed the amyloid precursor-like protein (APLP), appears to be similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are concentrated within three distinct regions of the two proteins where the identities are 47%, 54%, and 56%. The APLP cDNA hybridizes to two messages of approximately 2.4 and 1.6 kilobases that are present in mouse brain and neuroblastoma cells. Polyclonal antibodies raised against a peptide derived from the C terminus of APLP stain the cytoplasm in a pattern reminiscent of Golgi staining. In addition to APP, APLP also displays significant homology to the Drosophila APP-like protein APPL and a rat testes APP-like protein. These data indicate that the APP gene is a member of a strongly conserved gene family. Studies aimed at determining the functions of the proteins encoded by this gene family should provide valuable clues to their potential role in Alzheimer disease neuropathology.
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PMID:Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. 127 93

Amyloid beta-protein, the major constituent of amyloid plaques in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). Changes in the rates and or pathways of APP synthesis and degradation may be central to the deposition of beta-amyloid. We explored the possibility that APP processing is regulated by activation of endogenous cell-surface neurotransmitter receptors by stimulating C6, PC12 and neuroblastoma cells with the cholinergic agonist carbachol. We measured the intracellular APP in these cell lines by western blotting using three antibodies against different regions of APP. When cells were treated with carbachol for different periods, PC12 and C6 cells responded with a sharp decrease of APP bands. Similar blots probed with an antibody against heat-shock protein (HSP), showed no change in the intensity of the immunoreactive HSP-70 band. These results suggest that the decrease in intracellular APP seen after stimulation by carbachol has some specificity and that APP processing may be regulated by stimulation of cholinergic receptors on the surface of cells.
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PMID:The cholinergic agonist carbachol reduces intracellular beta-amyloid precursor protein in PC 12 and C6 cells. 128 95

Transmissible spongiform encephalopathies (prion diseases), Alzheimer's disease, and other amyloidoses result in the accumulation of certain abnormally stable proteins that are thought by many to play central roles in disease pathogenesis. Using scrapie-infected neuroblastoma cells as a model system, we found that Congo red, an amyloid-binding dye, potently inhibits the accumulation of the scrapie-associated, protease-resistant isoform of protein PrP without affecting the metabolism of the normal isoform. Growth of the cells with submicromolar concentrations of Congo red for 5 days reduced the amount of protease-resistant PrP detected in the cultures by greater than 90%. This activity of Congo red suggests that it selectively disrupts the conversion of PrP to the protease-resistant isoform or destabilizes this isoform once it is made. Potential therapeutic applications of Congo red are discussed.
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PMID:Potent inhibition of scrapie-associated PrP accumulation by congo red. 135 3

Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.
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PMID:Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. 135 34

We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry for the presence of protease inhibitors. Immunoreactivity for alpha 2-macroglobulin (alpha 2-M), the most potent of the known human protease inhibitors, was found in a subgroup of cortical and hippocampal AD senile plaques. In addition, large hippocampal neurons in AD brains displayed intracellular alpha 2-M immunoreactivity which was consistently stronger than in normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M behaves as an acute-phase protein in the nervous system. Therefore, we also examined AD brains for the presence of IL-6 and found strong immunostaining in and around a subgroup of senile plaques as well as around large cortical neurons. Only very few senile plaques also stained for C-reactive protein, an acute phase protein known to be inducible by IL-6. We propose that the presence of IL-6 and alpha 2-M immunoreactivity in AD brains is functionally linked and that a sequence of immunological events is part of the pathology of AD.
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PMID:Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. 137 Sep 67

Cerebrospinal fluid (CSF), serum and seminal plasma contain a small amount of SP-40,40, a modulatory protein of the human complement system. The SP-40,40 in each body fluid was different in molecular size on SDS-PAGE, and glioblastoma cells, hepatoma cells and testicular tumor cells produced SP-40,40, while neuroblastoma cells did not. Therefore, it was estimated that CSF SP-40,40 originated in glia cells, serum SP-40,40 in liver cells and seminal plasma SP-40,40 in testicular cells. SP-40,40 concentrations in CSF of the patients with Alzheimer's disease and the patients with cerebral tumor were higher than those of normal donors. beta-Amyloid deposits in the brains of the patients with Alzheimer's disease were stained with an anti-SP-40,40 monoclonal antibody (mAb) but not with an anti-S-protein mAb, while cellular processes around beta-amyloid were stained with an anti-S-protein mAb but not with an anti-SP-40,40 mAb. Therefore, beta-amyloid contained SP-40,40 in a form different from that in the soluble membrane attack complex (SMAC, SC5b-9) of the complement, which contains S-protein as well as SP-40,40.
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PMID:SP-40,40 is a constituent of Alzheimer's amyloid. 137 21

Patients with Alzheimer disease (AD) suffer mental deterioration associated with neurofibrillary tangle and senile plaque formation in the brain. Here we have determined the effects of brain extracts from normal and from AD patients on neuronal process formation by a pheochromocytoma (PC-12) and a neuroblastoma x glioma hybrid cell line (NG108-15). PC12 cells show a dose-related stimulation of branching of neuronal processes by AD brain extracts with cells cultured on a laminin substrate. The neurotrophic effects of extracts of AD brains may be related to the abnormal sprouting and neurofibrillary tangle formation observed in the brain in this disorder.
Alzheimer Dis Assoc Disord 1992
PMID:Alzheimer disease brain extract stimulates branching of laminin-mediated neuronal processes. 138 79

The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.
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PMID:Production of the Alzheimer amyloid beta protein by normal proteolytic processing. 143 60

We cloned, sequenced and characterized a promoter region of the mouse homologue of the Alzheimer's disease amyloid precursor protein (APP)-encoding gene. The promoter region is highly homologous to that of the human APP (hAPP) gene. It has a high G+C content, lacks typical 'TATA' and 'CAAT' boxes, and contains possible binding sites for AP-1, heat-shock factor, Sp1 and AP-4. The promoter region was fused with the cat reporter gene, and the fusion genes were transfected to both the NB41A3 (mouse neuroblastoma) and L-cell lines. The promoter activity was monitored by chloramphenicol acetyltransferase (CAT) activity in a transient expression assay. The promoter was equally active in both cell lines. The deletion analysis revealed that there existed a negative regulatory element(s) between -153 and -100 bp and a positive element(s) between -100 and -37 bp. The negative element was shown to suppress the transcriptional activity of heterologous simian virus 40 promoter. DNase I footprinting experiments revealed that three nuclear protein-binding sites existed in the regulatory region, one in the negative and two in the positive regulatory regions. Gel retardation assay showed that Sp1 was one of the factors binding to the positive regulatory region. A nuclear factor binding to the negative regulatory region seemed to be missing in brain.
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PMID:Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse. 155 68

1. beta-Amyloid precursor protein cross-reactive polypeptides were detected in the membrane extracts of a mouse neuroblastoma cell line, NB41A3. Four immunoreactive polypeptide bands were observed on western blots of a cell membrane extract. Their molecular weights as estimated by polyacrylamide gel electrophoresis ranged from 89.1 to 41 kDa. 2. After heparin affinity chromatography, two of these polypeptides strongly cross-reacted with an antibody that recognizes Alzheimer beta-amyloid precursor protein. 3. From the heparin binding fraction, these protein were further separated by reverse-phase high-performance liquid chromatography. A cross-reactive protein was isolated.
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PMID:A heparin-binding protein from neuroblastoma cells: immunological comparison to beta-amyloid precursor protein. 168 79


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