Abstract
Self-assembly of the 40/42 amino acid Aβ peptide is a key player in Alzheimers disease. Aβ40 is the most prevalent species, while Aβ42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Aβ monomer and a bent in this region could be the rate-limiting step in Aβ fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Aβ(21-30) and the monomers Aβ40 and Aβ42. On the basis of new simulations on dimers of full-length Aβ, we propose that the ratelimiting step involves the formation of a multimeric β-sheet spanning the central hydrophobic core (residues 17-21).
Keywords: Protein aggregation, simulations, Amyloid-beta, Alzheimer, coarse-grained model, structures, thermodynamics, monomer and dimer
Current Alzheimer Research
Title: Role of the Region 23-28 in Aβ Fibril Formation: Insights from Simulations of the Monomers and Dimers of Alzheimers Peptides Aβ40 and Aβ42
Volume: 5 Issue: 3
Author(s): Adrien Melquiond, Xiao Dong, Normand Mousseau and Philippe Derreumaux
Affiliation:
Keywords: Protein aggregation, simulations, Amyloid-beta, Alzheimer, coarse-grained model, structures, thermodynamics, monomer and dimer
Abstract: Self-assembly of the 40/42 amino acid Aβ peptide is a key player in Alzheimers disease. Aβ40 is the most prevalent species, while Aβ42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Aβ monomer and a bent in this region could be the rate-limiting step in Aβ fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Aβ(21-30) and the monomers Aβ40 and Aβ42. On the basis of new simulations on dimers of full-length Aβ, we propose that the ratelimiting step involves the formation of a multimeric β-sheet spanning the central hydrophobic core (residues 17-21).
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Cite this article as:
Melquiond Adrien, Dong Xiao, Mousseau Normand and Derreumaux Philippe, Role of the Region 23-28 in Aβ Fibril Formation: Insights from Simulations of the Monomers and Dimers of Alzheimers Peptides Aβ40 and Aβ42, Current Alzheimer Research 2008; 5 (3) . https://dx.doi.org/10.2174/156720508784533330
DOI https://dx.doi.org/10.2174/156720508784533330 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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