Amyloid oligomers and their membrane toxicity - A perspective study

Prog Biophys Mol Biol. 2024 Mar:187:9-20. doi: 10.1016/j.pbiomolbio.2024.01.002. Epub 2024 Jan 10.

Abstract

Amyloidosis is a condition involving a disparate group of pathologies characterized by the extracellular deposition of insoluble fibrils composed of broken-down proteins. These proteins can accumulate locally, causing peculiar symptoms, or in a widespread way, involving many organs and. causing severe systemic failure. The damage that is created is related not only to the accumulation of. amyloid fibrils but above all to the precursor oligomers of the fibrils that manage to enter the cell in a very particular way. This article analyzes the current state of research related to the entry of these oligomers into the cell membrane and the theories related to their toxicity. The paper proposed here not only aims to review the contents in the literature but also proposes a new vision of amyloid toxicity. that could occur in a multiphase process catalyzed by the cell membrane itself. In this process, the denaturation of the lipid bilayer is followed by the stabilization of a pore through energetically favorable self-assembly processes which are achieved through particular oligomeric structures.

Keywords: Amyloid fibrils; Amyloid oligomers; Amyloid toxicity; Membrane catalysis.

Publication types

  • Review

MeSH terms

  • Amyloid* / chemistry
  • Cell Membrane / metabolism
  • Lipid Bilayers* / metabolism

Substances

  • Amyloid
  • Lipid Bilayers