Elan's bapineuzumab could be highly synergistic with mtihtramycin and/or PEITC from watercress
"Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1.Christensen MA, Zhou W, Qing H, Lehman A, Philipsen S, Song W.
Department of Psychiatry, Brain Research Center, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Proteolytic processing of the beta-amyloid precursor protein (APP) at the beta site is essential to generate Abeta. BACE1, the major beta-secretase involved in cleaving APP, has been identified as a type 1 membrane-associated aspartyl protease. We have cloned a 2.1-kb fragment upstream of the human BACE1 gene and identified key regions necessary for promoter activity. BACE1 gene expression is controlled by a TATA-less promoter. The region of bp -619 to +46 is the minimal promoter to control the transcription of the BACE1 gene. Several putative cis-acting elements, such as a GC box, HSF-1, a PU box, AP1, AP2, and lymphokine response element, are found in the 5' flanking region of the BACE1 gene. Transcriptional activation and gel shift assays demonstrated that the BACE1 promoter contains a functional Sp1 response element, and overexpression of the transcription factor Sp1 potentiates BACE gene expression and APP processing to generate Abeta. Furthermore, Sp1 knockout reduced BACE1 expression. These results suggest that BACE1 gene expression is tightly regulated at the transcriptional level and that the transcription factor Sp1 plays an important role in regulation of BACE1 to process APP generating Abeta in Alzheimer's disease."
ncbi.nlm.nih.gov
mcb.asm.org
"...The treatment of mithramycin A resulted in a significant reduction of BACE1 promoter activity in a dose-dependent and time-dependent manner. Addition of 25, 75, and 125 nM mithramycin A for 48 h decreased the promoter activity to 89.10% ± 1.40%, 52.75% ± 1.74%, and 38.02% ± 4.24%, respectively (P < 0.001 by analysis of variance [ANOVA]) (Fig. 4E), of control levels, and 125 nM mithramycin A treatment for 16 and 48 h reduced the promoter activity to 79.55% ± 6.12% and 38.02% ± 4.24%, respectively (P < 0.001 by ANOVA) (Fig. 4F)..."
mcb.asm.org
Good luck and God bless,
George |
