New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC

Topic: Brain proteins, microglia and lab models

Recent data have allowed speculating that amyloid Aβ induces apoptosis via opening type-1 VDAC in cell membranes of hypo-metabolic neurons, a process most likely running over life time--as leaves fall from trees in the tropics--and ending in Alzheimer's disease whenever critical brain regions are affected. The expression of GxxxG motifs on either reactant under consideration is in line with this model of Alzheimer's disease pathogenesis, which clearly differs from the amyloid Aβ cascade theory, and which can, furthermore, be understood as a basic model for apoptosis induction. However, to assume randomly distributed interactions of body wide found amyloid Aβ peptides with the N-terminal voltage sensors of ubiquitously expressed cell membrane-standing human type-1 VDAC opens up a new view on Alzheimer's disease, which might even include a clue on systemic aspects of the disease. While elaborating this concept, my focus was at first only on the GxxxG motif at the proximal end of the N-terminal voltage sensor of type-1 VDAC. Here, I include a corresponding sequence stretch on the channel's β-sheet 19, too.

Key findings

• Recent data have allowed speculating that amyloid Aβ induces apoptosis via opening type-1 VDAC in cell membranes of hypo-metabolic neurons, a process most likely running over life time--as leaves fall from trees in the tropics--and ending in Alzheimer's disease whenever critical brain regions are affected.
• The expression of GxxxG motifs on either reactant under consideration is in line with this model of Alzheimer's disease pathogenesis, which clearly differs from the amyloid Aβ cascade theory, and which can, furthermore, be understood as a basic model for apoptosis induction.
• However, to assume randomly distributed interactions of body wide found amyloid Aβ peptides with the N-terminal voltage sensors of ubiquitously expressed cell membrane-standing human type-1 VDAC opens up a new view on Alzheimer's disease, which might even include a clue on systemic aspects of the disease.
• While elaborating this concept, my focus was at first only on the GxxxG motif at the proximal end of the N-terminal voltage sensor of type-1 VDAC.
• Here, I include a corresponding sequence stretch on the channel's β-sheet 19, too.

Why it matters

This paper proposes a model in which amyloid Aβ opens type-1 VDAC in cell membranes of hypo-metabolic neurons, leading to apoptosis and eventually Alzheimer's disease. This is a speculative model that differs from the amyloid cascade theory and reports no treatment or cure.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.ymgme.2013.01.008
• PubMed: 23419876
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{thinnes2013-23419876,
  author  = {Thinnes, F. P.},
  title   = {{New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC}},
  journal = {Molecular genetics and metabolism},
  year    = {2013},
  doi     = {10.1016/j.ymgme.2013.01.008},
  pmid    = {23419876},
  url     = {https://doi.org/10.1016/j.ymgme.2013.01.008}
}

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