Abstract
Self-assembly of the 40/42 amino acid Aβ peptide is a key player in Alzheimer's 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 rate-limiting step involves the formation of a multimeric β-sheet spanning the central hydrophobic core (residues 17-21). ©2008 Bentham Science Publishers Ltd.
| Original language | English |
|---|---|
| Pages (from-to) | 244-250 |
| Number of pages | 7 |
| Journal | Current Alzheimer Research |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 Jun 2008 |
| Externally published | Yes |
Keywords
- Alzheimer
- Amyloid-beta
- Coarse-grained model
- Monomer and dimer
- Protein aggregation
- Simulations
- Structures
- Thermodynamics
- amino acid
- amyloid beta protein
- amyloid beta protein[1-40]
- amyloid beta protein[1-42]
- dimer
- monomer
- Alzheimer disease
- beta sheet
- computer simulation
- hydrophobicity
- neurotoxicity
- prediction
- priority journal
- protein analysis
- protein assembly
- protein conformation
- protein folding
- protein structure
- review