The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins.
Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species a...
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2011-01-01
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doaj-fef77c23f66f4ebc902aca0310f27cd22020-11-24T21:48:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2490910.1371/journal.pone.0024909The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins.Claudia ManzoniLaura ColomboPaolo BiginiValentina DianaAlfredo CagnottoMassimo MessaMonica LupiValentina BonettoMauro PignataroCristina AiroldiErika SironiAlun WilliamsMario SalmonaAccumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1-40 and Aβ 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity.http://europepmc.org/articles/PMC3179491?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Claudia Manzoni Laura Colombo Paolo Bigini Valentina Diana Alfredo Cagnotto Massimo Messa Monica Lupi Valentina Bonetto Mauro Pignataro Cristina Airoldi Erika Sironi Alun Williams Mario Salmona |
spellingShingle |
Claudia Manzoni Laura Colombo Paolo Bigini Valentina Diana Alfredo Cagnotto Massimo Messa Monica Lupi Valentina Bonetto Mauro Pignataro Cristina Airoldi Erika Sironi Alun Williams Mario Salmona The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. PLoS ONE |
author_facet |
Claudia Manzoni Laura Colombo Paolo Bigini Valentina Diana Alfredo Cagnotto Massimo Messa Monica Lupi Valentina Bonetto Mauro Pignataro Cristina Airoldi Erika Sironi Alun Williams Mario Salmona |
author_sort |
Claudia Manzoni |
title |
The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
title_short |
The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
title_full |
The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
title_fullStr |
The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
title_full_unstemmed |
The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
title_sort |
molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Accumulation of β-sheet-rich peptide (Aβ) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. Aβ species are potent neurotoxins, however the molecular mechanism responsible for Aβ toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of Aβ 1-40 and Aβ 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that Aβ toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as Aβ receptors in N2a cells, triggering a multi factorial toxicity. |
url |
http://europepmc.org/articles/PMC3179491?pdf=render |
work_keys_str_mv |
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