The Proton-Pump Inhibitor Lansoprazole Enhances Amyloid Beta Production
Figure 4
Hypothetical mechanisms of lansoprazole on Aβ production.
Aβ peptides are produced from the consecutive cleavage of APP by BACE1 (β-secretase) and γ-secretase. The first cleavage generates soluble APPβ (sAPPβ) and the C99 C-terminal fragment, while the subsequent one releases Aβ peptides and the amyloid precursor protein intracellular domain (AICD). In basal conditions (left), a variety of Aβ species are formed. Conversely, when cells are treated with lansoprazole (right), BACE1 activity could be increased, generating more sAPPβ and C99 fragments and subsequently increasing the overall Aβ production. Lansoprazole also could act as an inverse GSM, shifting the γ–secretase cleavage, augmenting Aβ42 and reducing Aβ38. Together, lansoprazole is able to increase Aβ37, Aβ40 and Aβ42 species and decrease Aβ38.