Transient dynamics of Aβ contribute to toxicity in Alzheimer's disease.

TitleTransient dynamics of Aβ contribute to toxicity in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsHubin, E., N. A. J. van Nuland, K. Broersen, and K. Pauwels
JournalCell Mol Life Sci
Volume71
Issue18
Pagination3507-21
Date Published2014 Sep
ISSN1420-9071
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Brain, Humans, Models, Molecular, Protein Structure, Tertiary
Abstract

The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer's disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a harmless polypeptide into a malignant form that causes synaptotoxicity and neuronal cell death. Despite efforts to identify the toxic form of Aβ, the development of effective treatments for AD is still limited by the highly transient and dynamic nature of interconverting forms of Aβ. The variability within the in vivo "pool" of different Aβ peptides is another complicating factor. Here we review the dynamical interplay between various components that influence the heterogeneous Aβ system, from intramolecular Aβ flexibility to intermolecular dynamics between various Aβ alloforms and external factors. The complex dynamics of Aβ contributes to the causative role of Aβ in the pathogenesis of AD.

DOI10.1007/s00018-014-1634-z
Alternate JournalCell. Mol. Life Sci.
PubMed ID24803005
PubMed Central IDPMC4143600
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