Figure 2

Pharmacologic blockade of 5-lipoxygenase activating protein alters amyloid-β precursor protein metabolism via the γ-secretase pathway. (A) Representative western blots of APP, ADAM-10, BACE-1, secreted APPα, secreted APPβ, CTFs, PS1, nicastrin, APH-1 and Pen-2 in brain homogenates of Tg2576 mice receiving MK-591 or placebo for 8 months. (B) Densitometric analysis of some of the immunoreactivities to the antibodies shown in the previous panel (n = 9 control, n = 11 MK-591; *P <0.04). (C) Relative mRNA levels for BACE-1, PS1, nicastrin, APH-1 and Pen-2 in brain homogenates of Tg2576 mice receiving MK-591 or placebo for 8 months, as determined by real-time quantitative RT-PCR amplification (*P <0.02). (D) Representative western blot for total cAMP response element-binding and its phosphorylated form at Ser133, and Sp1 in brain homogenates of Tg2576 mice receiving MK-591 or placebo. (E) Densitometric analysis of the immunoreactivities to the antibodies shown in the previous panel (n = 9 control, n = 11 MK-591; *P <0.03). ADAM-10: disintegrin and metalloproteinase domain-containing protein 10; APH-1: anterior pharynx-defective 1; APP: amyloid-β precursor protein; BACE-1: β-site amyloid precursor protein cleaving enzyme 1; CREB: cAMP response element-binding protein; CTF: C-terminal fragments; Pen-2: presenilin enhancer 2; PS1: presenilin1; RT-PCR: reverse transcriptase polymerase chain reaction.