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.
(Less)
- author
- Benseny-Cases, Núria
; Klementieva, Oxana
LU
; Malý, Jan
and Cladera, Josep
- publishing date
- 2012-10
- type
- Contribution to journal
- publication status
- 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
- pmid:22272608
- 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
- 2024-07-23 02:03:45
@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}},
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}},
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}},
doi = {{10.2174/156720512803251129}},
volume = {{9}},
year = {{2012}},
}