Figure 1.

Possible mechanisms by which berberine modifies metabolism of APP.

Notes: In the amyloidogenic pathway, cleavage of APP by β-secretase generates soluble N-terminal fragment (sAPPβ) and C-terminal fragment (C99). C99 can be cleaved by γ-secretase to yield the APP intracellular domain (AICD) and Aβ. In the nonamyloidogenic pathway, α-secretase cleaves APP, generating a soluble fragment of APP (sAPPα) and C-terminal fragment (α-CTF), which is further cleaved by γ-secretase releasing the p3 peptide and AICD. BBR could decrease β-secretase and γ-secretase and inhibit the process of amyloidogenic pathway, lowering the Aβ release and the formation of amyloid plaques. The role of BBR in α-secretase remains unclear in the nonamyloidogenic pathway. ? Represent that the mechanism is unclear.

Abbreviations: BBR, berberine; Aβ, beta-amyloid; AICD, APP intracellular domain; APP, amyloid precursor protein; sAPP, soluble APP.