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

Wien Med Wochenschr. 2011 May;161(9-10):274-6. doi: 10.1007/s10354-011-0887-5. Epub 2011 Apr 4.

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.

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid beta-Peptides / genetics*
  • Apoptosis / genetics*
  • Aspartic Acid Endopeptidases / genetics
  • Cell Membrane / genetics
  • Humans
  • Models, Genetic
  • Neurons / metabolism
  • Peptide Fragments / genetics*
  • Protein Interaction Domains and Motifs / genetics*
  • Up-Regulation / genetics
  • Voltage-Dependent Anion Channel 1 / genetics*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • VDAC1 protein, human
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Voltage-Dependent Anion Channel 1
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human