title: Granular non-fibrillar aggregates and toxicity in Alzheimer's disease.
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.
authors.affiliation: Biophysics Unit and Centre of Studies in Biophysics, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Benseny-Cases
authors.forename: Oxana
authors.initials: O
authors.lastname: Klementieva
authors.forename: Jan
authors.initials: J
authors.lastname: Malý
authors.forename: Josep
authors.initials: J
authors.lastname: Cladera
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000502:physiology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)