757549.fig.007a
(a)
757549.fig.007b
(b)
Figure 7: BACE1 alternative splicing and targeting by antisense oligonucleotides. (a) Alternative splice sites in exons 3 and 4 of BACE1 mRNA. The amino acid length of each isoform upon translation to protein is indicated. Red lines indicate antisense oligonucleotides targeted to the normal 5′ and 3′ splice sites. (b) Structure of BACE1 showing the N- and C-terminal lobes, with the active site at the interface. Colored regions are parts of the full-length BACE1 enzyme that would be deleted in alternative splice isoforms. Note that these sites are in and around the active site and would be expected to affect the folding and final conformation of the enzyme.