Amyloid β binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway
Amyloid-β (Aβ) is a family of 36-43 amino-acids which form aggregates in the brains of Alzheimer's patients. The expression of Aβ has been linked to apoptosis in other studies, although the precise mechanism is poorly understood. For the first time, however, the authors of this study report that Aβ42 can actually inhibit apoptosis. Their experiments found that caspase activation and cell death induced by stauroporine (which activates the intrinsic pathway) was inhibited by Aβ42 somewhere between cytochrome c release and procaspase-9 activation. The authors suggest the mechanism is Aβ42 competing with Apaf-1 for procaspase-9 binding, which causes inhibition of the apoptosome. The effect was time-dependent (longer incubation times resulting in apoptosis), which suggests an initial transient period where the cell attempts to resist cell death in the presence of Aβ42. The effect was most prevalent in HeLa cells, but was also observed to a lesser extent in MG63 and SHSY5Y cell lines.