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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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

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

Volume 9 , Issue 8 , 2012

Page: [962 - 971] Pages: 10

DOI: 10.2174/156720512803251129

Price: $65

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.

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


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