Granular non-fibrillar aggregates and toxicity in Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

Granular non-fibrillar aggregates (GNAs) are identified as possible toxic species in Alzheimer's disease. GNAs form on the surface of negatively charged biological membranes and as a consequence of an acidic environment, off the polymerization pathway at neutral pH. Aβ (1-40) GNAs disturb the bilayer structure of model membranes and seem to be more toxic to cells with negatively charged membranes (consequence of chronic pre-apoptosis). GNAs may be relevant in physiological situations associated to Alzheimer's disease: a local acidic pH at the cell surface (consequence of lipid oxidation or other cell insults) and acidification as a consequence of vascular events causing hypoxia. Together with previous descriptions of granular aggregates with poly-glutamine peptides related to Huntington's disease and the SH3 domain of PI3, GNAs related to Alzheimer's disease are a further example of a possible common aggregation and toxicity mechanism in conformational diseases. GNAs may represent a new pharmacological target in Alzheimer's disease.

Details

Authors
External organisations
  • Autonomous University of Barcelona
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Neurosciences

Keywords

  • Alzheimer Disease/metabolism, Amyloid beta-Peptides/chemistry, Animals, Cell Membrane/chemistry, Flow Cytometry, Humans, Hydrogen-Ion Concentration, Lipid Peroxidation/physiology, Liposomes/chemistry, Microscopy, Atomic Force, Microscopy, Electron, Transmission, Neurons/metabolism, PC12 Cells, Peptide Fragments/chemistry, Rats
Original languageEnglish
Pages (from-to)962-71
Number of pages10
JournalCurrent Alzheimer Research
Volume9
Issue number8
Publication statusPublished - 2012 Oct
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes