Granular Non-Fibrillar Aggregates and Toxicity in Alzheimer’s Disease

Title:Granular Non-Fibrillar Aggregates and Toxicity in Alzheimer’s Disease

Volume: 9 Issue: 8

Author(s): Nuria Benseny-Cases, Oxana Klementieva, Jan Maly and Josep Cladera

Affiliation:

Keywords: Alzheimer’s, amyloid, membranes, non-fibrillar, pH, Electrophoresis, phosphatidylserine, lipid oxidation

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.

Cite this article as:

Benseny-Cases Nuria, Klementieva Oxana, Maly Jan and Cladera Josep, Granular Non-Fibrillar Aggregates and Toxicity in Alzheimer’s Disease, Current Alzheimer Research 2012; 9 (8) . https://dx.doi.org/10.2174/156720512803251129