Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer. s disease - a basic model of apoptosis?

Human type-1 porin/VDAC (voltage-dependent anion channel) carries a GxxxG motif in its N-terminal part, traversing the beta-barrel, while the Alzheimer. s disease (AD) rele-corresponding motifs close to their C-terminus. GxxxG motifs are established as aggregation/membrane perturbation motifs. These peptide primary structure data support a proposal I recently made on the basis of a synopsis of recent literature. Accordingly, amyloid Ab, cut from APP by beta-secretase BACE1 and gamma-secretase, has been insinuated to induce Alzheimer. s disease via apoptosis by opening type-1 porin/VDAC in cell membranes of hypometabolic neuronal cells. Considering the ubiquitous expression modus of APP, beta-and gamma-secretases and type-1 VDAC/eukaryotic porin a basic model of apoptosis might be given.