The molecular assembly of amyloid Aβ controls its neurotoxicity and binding to cellular proteins
Articolo
Data di Pubblicazione:
2011
Citazione:
The molecular assembly of amyloid Aβ controls its neurotoxicity and binding to cellular proteins / C. Manzoni, L. Colombo, P. Bigini, V. Diana, A. Cagnotto, M. Messa, M. Lupi, V. Bonetto, M. Pignataro, C. Airoldi, E. Sironi, A. Williams, M. Salmona. - In: PLOS ONE. - ISSN 1932-6203. - 6:9(2011), pp. e24909.1-e24909.8.
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
amyloid beta-peptides; animals; blotting, far-western; cathepsin D; cell line, tumor; cell survival; cytoplasm; cytoskeleton; endoplasmic reticulum; heat-shock proteins; humans; immunohistochemistry; lysosomes; microscopy, fluorescence; peptide fragments; protein binding; protein multimerization; vimentin; agricultural and biological sciences (all); biochemistry, genetics and molecular biology (all); medicine (all)
Elenco autori:
C. Manzoni, L. Colombo, P. Bigini, V. Diana, A. Cagnotto, M. Messa, M. Lupi, V. Bonetto, M. Pignataro, C. Airoldi, E. Sironi, A. Williams, M. Salmona
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