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

Benseny-Cases, Núria; Klementieva, Oxana LU ; Malý, Jan and Cladera, Josep (2012) In Current Alzheimer Research 9(8). p.71-962
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... (More)

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.

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published
subject
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
in
Current Alzheimer Research
volume
9
issue
8
pages
10 pages
publisher
Bentham Science Publishers
external identifiers
  • scopus:84867721914
ISSN
1875-5828
DOI
10.2174/156720512803251129
language
English
LU publication?
no
id
120353ae-dac7-4ff9-9637-f56b3085ac16
date added to LUP
2018-11-01 13:30:53
date last changed
2019-08-14 04:26:27
@article{120353ae-dac7-4ff9-9637-f56b3085ac16,
  abstract     = {<p>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.</p>},
  author       = {Benseny-Cases, Núria and Klementieva, Oxana and Malý, Jan and Cladera, Josep},
  issn         = {1875-5828},
  keyword      = {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},
  language     = {eng},
  number       = {8},
  pages        = {71--962},
  publisher    = {Bentham Science Publishers},
  series       = {Current Alzheimer Research},
  title        = {Granular non-fibrillar aggregates and toxicity in Alzheimer's disease},
  url          = {http://dx.doi.org/10.2174/156720512803251129},
  volume       = {9},
  year         = {2012},
}