Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presenilin 1 (PS 1) shows missense mutations in most early-onset familial Alzheimer's disease (FAD). Transfection of cDNA for wild type PS 1 into rat pheochromocytoma PC12 cells generated a 47 kDa full-size PS 1 protein, which was processed into a 28 kDa N-terminal fragment and a 19 kDa C-terminal fragment. We prepared selected Alzheimer-associated mutations (Gly384Ala, Leu392Val, and Cys410Tyr) of PS 1, which localized after a possible cleavage site. By transient expression in PC12 cells and rat glioma cell line, C6, we examined their influence on the processing of PS 1. Cys410Tyr inhibited proteolytic processing of PS 1, while Gly384Ala and Leu392Val did not. Thus, the Alzheimer related mutations can be divided into two groups in terms of their effect on the proteolytic cleavage of PS 1.
 ...
PMID:Different effects of Alzheimer-associated mutations of presenilin 1 on its processing. 922 2

Analysis of 139 CSF samples from living subjects, using iso-electric focusing in polyacrylamide gels, demonstrated an anomalous molecular form of acetylcholinesterase (AChE). This form was present in 84 of 87 patients with a clinical diagnosis of Alzheimer's disease (AD), 28 of whom have died and in whom histopathological confirmation of AD was obtained. The abnormal AChE form was also present in 22 of 23 patients with clinical dementia not regarded as AD type. In the six patients who died this abnormal AChE form was found in three cases of multi-infarct dementia, one with cerebral glioma with dementia and one with clinical dementia, but no pathology was found based on the Khachaturian criteria for AD. One patient with normal pressure hydrocephalus was negative when tested for the abnormal AChE form. This evidence indicates that the anomalous molecular form of AChE may not be specific for AD, and may possibly be a common indicator for organic dementia. The discovery of this form in 27 of 29 age-matched non-demented controls may indicate that the anomalous molecular form of AChE may not only exist in patients with clinically detectable dementia, but is probably present for a period before the onset of dementia. Recognizing and understanding the existence of pre-clinical dementia would be beneficial in designing a strategy for both the prevention and the treatment of dementia.
 ...
PMID:An CSF anamalous molecular form of acetylcholinesterase in demented and non-demented subjects. 935 48

Matrix metalloproteinases (MMPs) are increasingly being implicated in the pathogenesis of several CNS diseases. In multiple sclerosis, MMPs could be responsible for the influx of inflammatory mononuclear cells into the CNS, contribute to myelin destruction and disrupt the integrity of the blood-brain barrier; in Alzheimer's disease, MMPs might mediate the deposition of amyloid beta-proteins; and MMPs are known to contribute to the invasiveness of malignant glioma cells and might regulate their angiogenic capacity. Nonetheless, MMPs could also have beneficial roles in recovery from CNS injury.Therefore, both the identity of the MMP and its cellular origin could determine whether disease pathogenesis or regeneration occurs, and thus synthetic MMP inhibitors might be valuable for treating some CNS diseases.
 ...
PMID:Matrix metalloproteinases and diseases of the CNS. 1126 39

Cyclooxygenase-2 (COX-2; EC 1.14.99.1) RNA message abundance in 25 control and Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-confirmed sporadic Alzheimer's disease (AD) brains is remarkably heterogeneous when compared with 55 other AD brain RNA message levels that were previously characterized (Lukiw and Bazan: J Neurosci Res 50:937-945, 1997). Examination of nuclear protein extracts (NPXTs) that were derived from control and AD-affected brain neocortical nuclei (n = 20; age range, 60-82 years; postmortem interval, 0.5-6.5 hours) by using gel shift, gel supershift, and cold oligonucleotide competition assay revealed a highly significant relationship between the extent of inflammatory transcription factor, nuclear factor (NF)-kappaB: DNA binding and the abundance of the COX-2 RNA signal (P < 0.0001; analysis of variance). No strong correlation with AP-1-DNA binding was noted (P > 0.045). These data are the first linking inflammation-related transcription factor NF-KB-DNA binding to up-regulation of transcription from a key inflammatory gene, COX-2, in both normally aging brain and in AD-affected neocortex. Systematic deletion of NF-KB-DNA binding sites in human COX-2 promoter constructs attenuates COX-2 transcriptional induction by mediators of inflammation. Strong NF-kappaB-DNA binding has been reported previously to temporally precede COX-2 gene transcription in human epithelial (A549), hamster B-cell (HIT-T15), human endothelial (HUVEC), human lymphoblast (IM9), human fibroblast (IMR90), rat glioma/mouse neuroblastoma (NG108-15), human keratinocyte (NHEK), mouse fibroblast (NIH 3T3), rat neuroblastoma (SH-SY5Y) cell lines and in mouse and rat brain hippocampus, indicating a highly conserved inflammatory signaling pathway that is common to diverse species and cell types. The mouse, rat, and human COX-2 immediate promoters, despite 7.5 x 10(7) years of DNA sequence divergence, each retain multiple recognition sites specific for NF-kappaB-DNA binding. These data suggest that basic gene induction mechanisms, which have been conserved over long periods of evolution, that increase NF-kappaB-DNA binds ing may be fundamental in driving transcription from inflammation-related genes, such as COX-2, that operate in stressed tissues, in normally aging cell lines, and in neurodegenerative disorders that include AD brain.
 ...
PMID:Strong nuclear factor-kappaB-DNA binding parallels cyclooxygenase-2 gene transcription in aging and in sporadic Alzheimer's disease superior temporal lobe neocortex. 972 29

Mutations in the presenilin 1 (PS-1) gene account for most cases of autosomal dominant early-onset familial Alzheimer's disease (AD). In order to elucidate the cellular expression profile of PS-1 we used a novel N-terminal monoclonal antibody against human PS-1. Immunohistochemical staining was observed strongly in senile plaques, and reactive astrocytes of gray and white matter. Neuronal immunoreactivity, however, was found to be only moderate. RT-PCR analysis of PS-1 mRNA revealed expression throughout human development as well as in human glioma cell lines. Altered PS-1 function may contribute to plaque formation in AD.
 ...
PMID:Prominent expression of presenilin-1 in senile plaques and reactive astrocytes in Alzheimer's disease brain. 983 64

The relevance of transglutaminases with neural function and several disorders has been emphasized recently. Especially, many polypeptides associated with neurodegenerative diseases are suggested to be putative transglutaminase substrates such as beta amyloid protein of Alzheimer's disease, microtubule-associated proteins and neurofilaments, etc. In addition, the CAG repeated gene products with probable polyglutamine tract, putative transglutaminase substrates, were identified in several neurodegenerative disorders. However, the identity of the brain transglutaminase has not been confirmed, because of enzymic stability and low activity. In the present experiment, we have isolated brain-specific transglutaminases, designated as TGase NI and TGase NII, which are different from other types of transglutaminases in respects of molecular weights (mw. 45 kDa, 29 kDa respectively), substrate affinity, elution profile on ion-exchange chromatography, sensitivity to proteases and ethanol, and immunological properties. The enzymes were localized specifically in the brain tissues but not in the liver tissue. And neural cells such as pheochromocytoma cell, glioma cell, primary neuronal and glial cells were shown to be enriched with TGase NI and TGase NII. The possible biological roles of the enzymes were discussed not only on the aspect of crosslinking activity but also of signal transducing capacity of the enzyme in the brain.
 ...
PMID:Isolation and characterization of brain-specific transglutaminases from rat. 989 46

Many cases of early-onset familial Alzheimer's disease have been linked to mutations within two genes encoding the proteins presenilin-1 and presenilin-2. The presenilins are 48-56-kDa proteins that can be proteolytically cleaved to generate an N-terminal fragment (approximately 25-35 kDa) and a C-terminal fragment (approximately 17-20 kDa). The N- and C-terminal fragments of presenilin-1, but not full-length presenilin-1, were readily detected in both human and mouse cerebral cortex and in neuronal and glioma cell lines. In contrast, presenilin-2 was detected almost exclusively in cerebral cortex as the full-length molecule with a molecular mass of 56 kDa. The association of the presenilins with detergent-insoluble, low-density membrane microdomains, following the isolation of these structures from cerebral cortex by solubilization in Triton X-100 and subsequent sucrose density gradient centrifugation, was also examined. A minor fraction (10%) of both the N- and C-terminal fragments of presenilin-1 was associated with the detergent-insoluble, low-density membrane microdomains, whereas a considerably larger proportion of full-length presenilin-2 was present in the same membrane microdomains. In addition, a significant proportion of full-length presenilin-2 was present in a high-density, detergent-insoluble cytoskeletal pellet enriched in beta-actin. The presence of the presenilins in detergent-insoluble, low-density membrane microdomains indicates a possible role for these specialized regions of the membrane in the lateral separation of Alzheimer's disease-associated proteins within the lipid bilayer and/or in the distinct functions of these proteins.
 ...
PMID:Characterization of detergent-insoluble complexes containing the familial Alzheimer's disease-associated presenilins. 1009 59

Hydrogen peroxide has been suggested to play an important role in the pathogenesis of Alzheimer's disease. In the present study, the effects of hydrogen peroxide upon the functional integrity of beta-adrenoceptors have been investigated in C6 glioma cells. Treatment of cells for 24 h with hydrogen peroxide in serum-free medium produced a concentration-dependent cell toxicity, seen both using cell counting and LDH release into medium as end point. There were no large nor consistent changes in either the density of cell surface beta 1, or beta 2-adrenoceptors, measured using the hydrophilic ligand [3H](-)-CGP 12177, nor in either basal, forskolin and isoprenaline-stimulated cAMP responses, following hydrogen peroxide treatment. It is concluded that the decreased adenylyl cyclase activity and responsiveness to Gs stimulation found in post-mortem brain samples from Alzheimer's disease autopsy cases is unlikely to be mediated by hydrogen peroxide.
 ...
PMID:The effect of hydrogen peroxide upon beta-adrenoceptor density and function in C6 rat glioma cells. 1010 Jan 97

Because distinct mutations in presenilin 1 and presenilin 2 are a major cause of early-onset familial Alzheimer's disease, we generated four monoclonal antibodies for the identification, localization, and investigation of presenilins in various cell lines and tissues from patients and controls. We show that these antibodies are specific for the N- and C-terminal domains of human presenilin 1 and presenilin 2. They recognize presenilin full-length proteins and their approximately 28-35 kDa N-terminal fragments and approximately 18-20 kDa C-terminal fragments. None of the antibodies showed cross-reaction in their specific detection ability. We demonstrated that presenilin 1 and presenilin 2 are proteolytically processed in human glioma cell lines, transfected and untransfected human neuroblastoma SH-SY5Y cells, COS-7 cells, rat cerebellar neuronal ST15 cells, mouse and human brain. Remarkably, we observed that presenilin 2 is alternatively cleaved during apoptosis, producing smaller C-terminal fragments. By analyzing the subcellular distribution of presenilins, we found reticular and fine vesicular staining throughout the cell bodies. In addition, staining of Golgi compartments and the perinuclear envelope was observed. Alzheimer's disease brain showed strong immunoreactivity of presenilin 1 in reactive astrocytes and senile plaques. This high expression of presenilin 1 may explain the increased production and accumulation of the amyloid-beta peptide in patients with sporadic Alzheimer's disease in the absence of familial presenilin mutation.
 ...
PMID:Analysis of presenilin 1 and presenilin 2 expression and processing by newly developed monoclonal antibodies. 1034 Jul 48

Aluminum, a trivalent cation unable to undergo redox reactions, has been linked to many diseases such as dialysis dementia and microcytic anemia without iron deficiency. It has also been implicated in Alzheimer's disease although this is controversial. Because cell death due to oxidative injury is suspected to be a contributory factor in many neurological diseases and aluminum neurotoxicity, glioma (C-6) and neuroblastoma (NBP2) cells were utilized to assess early changes in oxidative parameters consequent to a 48-h exposure to aluminum sulfate. A 500-microM concentration of this salt produced a significant increase in reactive oxygen species (ROS) production and a significant decrease in glutathione (GSH) content in glioma cells. However, the same concentration of the aluminum salt did not lead to any significant changes in the neuroblastoma cells. Mitochondrial respiratory activity in glioma cells was also found to be significantly higher in the aluminum treated cells. As judged by morin-metal complex formation, aluminum can enter glioma cells much more readily than neuroblastoma cells. Thus, it is possible that the cerebral target following an acute exposure to aluminum may be glial rather than neuronal.
 ...
PMID:Aluminum-induced oxidative events in cell lines: glioma are more responsive than neuroblastoma. 1038 Nov 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>