Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presenilin-1 (PS-1) gene on chromosome 14 carries mutations which cosegregate with early-onset familial Alzheimer's disease. We quantified PS-1 mRNA in post-mortem mid-temporal and superior frontal cortices from 14 Alzheimer's disease subjects, 9 non-demented controls and 5 subjects with other neurological diseases using solution hybridisation-RNase protection assay. APP and APLP2 mRNAs had previously been quantified in these samples (Johnston et al. (1996) Mol. Brain Res., in press) and subjects were apolipoprotein E (APOE) genotyped. There were no significant differences between PS-1 mRNA levels per pg total RNA in mid-temporal or superior frontal cortices of the Alzheimer's disease subjects, compared to controls. PS-1 mRNA levels corresponded to 10% of total APP and 30% of APLP2 mRNA levels, and were not significantly affected by age, post-mortem delay, tissue pH, or APOE genotype. PS-1 mRNA showed significant positive correlations with APP and APLP2 mRNA levels in mid-temporal cortex and with APP mRNA in superior frontal cortex. This may reflect a co-regulation of the expression of these genes, or the fact that they are expressed in similar neuronal populations.
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PMID:Quantification of presenilin-1 mRNA in Alzheimer's disease brains. 883 Jun 58

Amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) are members of a multigene family of proteins implicated in the pathogenesis of Alzheimer's disease. We describe the development of an RNA-RNA solution hybridisation-RNase protection assay to quantify APP mRNA. APP mRNA splice forms containing the Kunitz-type protease inhibitor (KPI) insert, and APLP2 mRNA in total nucleic acid extracts from a range of tissue types. Solution hybridisation-RNase protection assay enables absolute quantification of target mRNA, by conversion of the hybridisation signal to pg mRNA using a standard curve. The assay is sensitive, capable of detecting 1 pg target mRNA, and reproducible, with an inter-assay variability of less than 10% and an intra-assay variability of 3-4%. We quantified APP and APLP2 mRNA in cell lines and post-mortem human brain tissue samples. To test whether we could detect physiological differences in APP mRNA levels, a fibroblast cell line with a paternal chromosome 21 deletion of the region including the APP gene was analysed and found to express half as much APP mRNA as control fibroblasts. In addition, a reversible, approx. 30% increase in APP mRNA levels was detected in human lymphoblastoid cell lines following heat shock, a physical stimulus previously shown to increase APP expression. Regional differences in the expression of APP and APLP2 were seen in human post-mortem cerebral cortex and cerebellum. Levels of APP and APLP2 mRNA were highest in the temporal cortex, slightly lower in frontal and occipital cortices, and lowest in the cerebellum. The highest proportion of KPI-containing APP was seen in the frontal and temporal cortices. The ratio of APP:APLP2 mRNA was 1:0.3 in the cortical tissue and 1:0.8 in the cerebellum. In conclusion, quantitative solution hybridisation-RNase protection assay of total APP. APP KPI and APLP2 mRNA provides a new tool to improve the resolution of studies of potentially subtle alterations in the expression of these genes in both cell culture model systems and Alzheimer's disease post-mortem human brain tissue.
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PMID:A new quantitative solution hybridisation-RNase protection assay for APP and APLP2 mRNA. 903 21

Amyloid precursor protein (APP) is metabolised to produce A beta, a peptide found aggregated in Alzheimer's disease neuritic plaques. APP is a member of a multigene protein family which includes amyloid precursor-like protein 2 (APLP2). Since A beta accumulation can be triggered by factors acting up- or downstream of APP processing, we investigated whether APP mRNA expression was altered in Alzheimer's disease post-mortem cerebral cortex. In addition, we characterised cortical APLP2 mRNA levels. Quantitative RNA-RNA solution hybridisation-RNase protection was used to assay total APP. APP containing the Kunitz-type protease inhibitor (KPI) insert and APLP2 mRNA in mid-temporal and superior frontal cortices from apolipoprotein E-genotyped subjects with Alzheimer's disease, other neurological diseases and non-demented controls. Approximately 3 times more APP than APLP2 mRNA was detected and about 70% of total APP mRNA contained the KPI insert in the control subjects. Total APP and APLP2 mRNA levels were significantly reduced in Alzheimer's disease mid-temporal, but not superior frontal cortex, suggesting that regional reductions in these mRNA correlate with severity of disease pathology. A small significant increase in the proportion of APP KPI mRNA was seen in both cortical regions in Alzheimer's disease. Apolipoprotein E genotype did not influence cortical levels of total APP, APP KPI or APLP2 mRNA. Alzheimer's disease-related increases in tissue DNA content were seen in both regions studied, while tissue RNA levels were reduced in the positive disease controls. In summary, these results indicate that Alzheimer's disease is not associated with over-expression of either APP or APLP2 mRNA. Our findings reveal a disease-associated increase in the proportion of APP KPI-containing isoforms, and further investigation should clarify whether this predisposes affected individuals to A beta production and aggregation, or reflects later events such as gliosis and neuronal cell death.
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PMID:Quantification of APP and APLP2 mRNA in APOE genotyped Alzheimer's disease brains. 903 22

The presenilin-1 (PS-1) and amyloid precursor protein (APP) genes carry mutations which co-segregate with early-onset familial Alzheimer's disease. The APP and PS-1 gene products may be involved in the aetiology of the more common late onset form of Alzheimer's disease, where increasing age is a major risk factor. To investigate whether age affected mRNA expression of these genes, we quantified PS-1, total APP, APP containing the kunitz-type protease inhibitor (KPI) domain and amyloid precursor-like protein 2 (APLP2) mRNAs in post-mortem superior frontal cortices from 23 control subjects aged 38 to 89 years using solution hybridisation-RNase protection assays. PS-1, total APP, APP KPI and APLP2 mRNA levels were unchanged over this age range. PS-1 was the least abundant mRNA, at approximately 7% of total APP, the most highly expressed mRNA studied (10.8 copies/pg total RNA). The proportion of total APP encoding the KPI domain (approximately 52%) was unaffected by age. APLP2 mRNA was present at approximately 29% of the total APP mRNA level. Significant positive correlations were present between total APP, APP KPI and APLP2 mRNA levels. These results indicate that the increased prevalence of Alzheimer's disease cannot be attributed to alterations in cortical PS-1, APP and APLP2 mRNA levels or APP KPI splicing during aging.
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PMID:Presenilin-1, amyloid precursor protein and amyloid precursor-like protein 2 mRNA levels in human superior frontal cortex during aging. 938 85