r(HGNC:BACE1)
However, a recent study blocking the conversion of testosterone to estrogen found an estrogen-independent improvement in cognitive function and lowering of plaque formation along with a decrease in BACE1 mRNA, protein level, and activity [211]. In addition, testosterone may also reduce the protein level of PS1 [196] PubMed:21214928
As expected, TNFα greatly stimulated BACE-1 transcription whereas anatabine fully prevented the increase in BACE-1 mRNA levels induced by TNFα (Fig. 7A). PubMed:21958873
Additionally, we found that Bace1 mRNA expression is significantly increased in the brain of Tg PS1/APPswe mice compared to wild- type littermates, whereas a significant reduction in Bace1 mRNA levels is observed in Tg PS1/ APPswe receiving 20 mg/Kg/Day of anatabine in their drinking water showing that at this dosage anatabine can mitigate the upregulation of Bace1 expression in Tg PS1/APPswe mice (Fig 9). PubMed:26010758
Additionally, we found that Bace1 mRNA expression is significantly increased in the brain of Tg PS1/APPswe mice compared to wild- type littermates, whereas a significant reduction in Bace1 mRNA levels is observed in Tg PS1/ APPswe receiving 20 mg/Kg/Day of anatabine in their drinking water showing that at this dosage anatabine can mitigate the upregulation of Bace1 expression in Tg PS1/APPswe mice (Fig 9). PubMed:26010758
We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948
We found that both (-)-nilvadipine and racemic nilvadipine reduce BACE-1 mRNA expression (Fig. 1C) induced by TNFα PubMed:25331948
We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948
We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948
It is interesting to note that miR‐124 has a target sequence on BACE1 mRNA, and by binding to it, it inhibits mRNA. PubMed:30663117
For instance, measuring lncRNA BACE1 within the cytoplasm of the patients showed that its level in patients with Alzheimer’s was significantly higher than that in the control group PubMed:30663117
BACE1‐AS can increase the expression of BACE1 mRNA by increasing its stability, which gives rise to AD PubMed:30663117
Compared to controls, TNF-a treatment resulted in significant increase in luciferase activity in the cells transfected with the human BACE1 promoter pB1P- N1 plasmid (p<0.005) and addition of aspirin in- hibited the BACE1 transcriptional activation induced by TNF-a (p<0.005 relative to TNF-a and p>0.05 relative to controls) (Fig. 6a). PubMed:21329555
Consistent with pB1P-N1 plasmid results, TNF-a significantly induced BACE1-NF-kB promoter activation (p<0.005) and the NSAIDs aspirin, ibuprofen and indomethacin significantly blocked the TNF-a-induced BACE1- NF-kB promoter activation (p<0.005) (Fig. 6b). PubMed:21329555
Consistent with pB1P-N1 plasmid results, TNF-a significantly induced BACE1-NF-kB promoter activation (p<0.005) and the NSAIDs aspirin, ibuprofen and indomethacin significantly blocked the TNF-a-induced BACE1- NF-kB promoter activation (p<0.005) (Fig. 6b). PubMed:21329555
Our data clearly demonstrate that NSAIDs inhibit TNF-a-induced BACE1 transcription via its NF-kB cis-acting elements. PubMed:21329555
Consistent with pB1P-N1 plasmid results, TNF-a significantly induced BACE1-NF-kB promoter activation (p<0.005) and the NSAIDs aspirin, ibuprofen and indomethacin significantly blocked the TNF-a-induced BACE1- NF-kB promoter activation (p<0.005) (Fig. 6b). PubMed:21329555
These results suggest that the 4NF-kB oligonucleotides con- taining four putative NF-kB-binding elements from the human BACE1 promoter is able to respond to NF-kB signalling to modulate a downstream gene transcription. PubMed:21329555
Our data clearly demonstrate that NSAIDs inhibit TNF-a-induced BACE1 transcription via its NF-kB cis-acting elements. PubMed:21329555
Consistent with our Western blot results, a significant elevation of promoter activity was detected in cells co- expressing BACE1 reporter plasmid and NF-kB p65 (Fig. 3d). PubMed:21329555
When wild-type cells were transfected with NF-kB p65 expression plasmid, the mRNA level of BACE1 was elevated by 476.6¡21.68% (p<0.0001 relative to controls) (Fig. 5b). PubMed:21329555
Compared to controls, TNF-a treatment resulted in significant increase in luciferase activity in the cells transfected with the human BACE1 promoter pB1P- N1 plasmid (p<0.005) and addition of aspirin in- hibited the BACE1 transcriptional activation induced by TNF-a (p<0.005 relative to TNF-a and p>0.05 relative to controls) (Fig. 6a). PubMed:21329555
Consistent with pB1P-N1 plasmid results, TNF-a significantly induced BACE1-NF-kB promoter activation (p<0.005) and the NSAIDs aspirin, ibuprofen and indomethacin significantly blocked the TNF-a-induced BACE1- NF-kB promoter activation (p<0.005) (Fig. 6b). PubMed:21329555
Further- more, naproxen and ibuprofen and perhaps other NSAIDs, can block the inflammation-induced BACE1 transcription and Aβ production [52,87]. PubMed:27288790
Further- more, naproxen and ibuprofen and perhaps other NSAIDs, can block the inflammation-induced BACE1 transcription and Aβ production [52,87]. PubMed:27288790
Disruption of NF-κB p65 expression in RelA-KO cells abolished GSK3β's effect on the transcriptional activation of the human BACE1 gene promoter. PubMed:27288790
BACE1-AS regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. PubMed:27288790
Upon exposure to various cell stressors including Aβ 42 , expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Aβ 42 through a post-transcriptional feed-forward mechanism [74]. PubMed:27288790
For instance, measuring lncRNA BACE1 within the cytoplasm of the patients showed that its level in patients with Alzheimer’s was significantly higher than that in the control group PubMed:30663117
BACE1‐AS can increase the expression of BACE1 mRNA by increasing its stability, which gives rise to AD PubMed:30663117
BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.
If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.