Fig. 2
From: Therapeutic potential of ADAM10 modulation in Alzheimer’s disease: a review of the current evidence
The amyloidogenic and non-amyloidogenic pathways of APP processing. In amyloidogenic pathway, BACE1 affects APP leading to release sAPPβ. γ-secretase is the other protease involved in amyloidogenic pathway, which its activity contributes to Aβ formation. In the non-amyloidogenic pathway, at the first step, ADAM10 cleaves APP leading to release sAPPα. At the second step, γ-secretase activity leads to P3 fragment formation and release. On the other hand, ADAM10 cleaves TREM2 leading to release soluble TREM2, which binds to Aβ plaque and induces its clearance. The PI3K/AKT and ERK1/2 pathways are involved in regulation of ADAM10 expression. This effect can be mediated by CREB and HIF-1. Aβ: amyloid β; ADAM10: a disintegrin and metalloproteinase domain-containing protein 10; APP: amyloid precursor protein; BACE1: beta-site amyloid precursor protein cleaving enzyme-1; CREB: cAMP response element-binding protein; ERK1/2: extracellular signal‑regulated protein kinase 1/2; HIF-1: hypoxia inducible factor 1; PI3K: phosphatidylinositol 3 kinase; TREM2: triggering receptor expressed on myeloid cells 2