title: Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis?
abstract: Human type-1 porin/VDAC (voltage-dependent anion channel) carries a GxxxG motif in its N-terminal part, traversing the β-barrel, while the Alzheimer's disease (AD) relevant amyloid peptides Aβ1-42 and Aβ1-40 show a series of 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 Aβ, 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.
authors: futhin@t-online.de
authors: Friedrich P
authors: FP
authors: Thinnes
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C494762:VDAC1 protein, human; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D050995:Voltage-Dependent Anion Channel 1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human