Soluble amyloid precursor protein alpha (sAPPα) ameliorates matrix-metalloproteinase inhibitor-induced proliferation deficits in neural progenitor cells (NPCs). (a) Western blot analysis shows that levels of secreted sAPP are dramatically reduced in NPCs after treatment with matrix-metalloproteinase inhibitor GM6001 (GM) when compared with NPCs treated with an inactive inhibitor (NC). Actin from cell lysate was used as a control for protein load. (b) Optical density of expression intensity of sAPP normalized to actin. (c) NPC proliferation as assayed by a clonogenic assay. Total number of NPCs after 10 days in culture is reduced by GM6001 in a dose-dependent manner. Red diamond indicates 1 μM NC, blue diamonds indicate GM6001, green diamond indicates 1 μM GM6001 + 10 nM sAPPα, and dotted line indicates the number of cells originally plated. (d) Recombinant sAPPα (10 nM) can recover 1 μM GM6001-induced deficits in NPC proliferation as shown by a reduction in the number of NPCs counted per neurosphere observed in a clonogenic assay. (e) Measure of neurosphere diameter of neurospheres formed after a 10-day clonogenic assay in which NPCs were treated with 1 μM NC, 1 μM GM6001, or 1 μM GM6001 + 10 nM sAPPα. (f) The number of neurospheres formed after a 10-day clonogenic assay in which NPCs were treated with 1 μM NC, 1 μM GM6001, or 1 μM GM6001 + 10 nM sAPPα. (g) Dose response of sAPPα effect on NPC proliferation after inhibition with 1 μM GM6001 in a clonogenic assay. Red diamond indicates 1 μM NC, blue diamond indicates 1 μM GM6001, and green diamonds indicate recombinant sAPPα. Error bars represent standard error of the mean. *P < 0.05, analysis of variance with post hoc analysis. A.U., arbitrary units.