ArticleACS chemical neuroscience2011
Molecular engineering of a secreted, highly homogeneous, and neurotoxic aβ dimer.
Article in ACS chemical neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- A Disulfide-Stabilized Aβ that Forms Dimers but Does Not Form Fibrils.Biochemistry · 2022Article
- Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Emergence of Barrel Motif in Amyloid-β Trimer: A Computational Study.The journal of physical chemistry. B · 2020Article
- IPSC-Derived Neuronal Cultures Carrying the Alzheimer's Disease AssociatedInternational journal of molecular sciences · 2020Article
- Discrete Pools of Oligomeric Amyloid-β Track with Spatial Learning Deficits in a Mouse Model of Alzheimer Amyloidosis.The American journal of pathology · 2018Article
- Aβ42 pentamers/hexamers are the smallest detectable oligomers in solution.Scientific reports · 2017Article
- Conformational Ensembles of the Wild-Type and S8C Aβ1-42 Dimers.The journal of physical chemistry. B · 2017Article
- Role of the N-terminus for the stability of an amyloid-β fibril with three-fold symmetry.PloS one · 2017Article
- The Aggregation Paths and Products of Aβ42 Dimers Are Distinct from Those of the Aβ42 Monomer.Biochemistry · 2016Article
- Coupling of Zinc-Binding and Secondary Structure in Nonfibrillar Aβ40 Peptide Oligomerization.Journal of chemical information and modeling · 2015Article
- Synthetic dimeric Aβ(28-40) mimics the complex epitope of human anti-Aβ autoantibodies against toxic Aβ oligomers.The Journal of biological chemistry · 2013Article
- Glial cells in (patho)physiology.Journal of neurochemistry · 2012Review
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Aβ oligomers play a key role in the pathophysiology of Alzheimer's disease. Research into structure-function relationships of Aβ oligomers has been hampered by the lack of large amounts of homogeneous and stable material. Using computational chemistry, we designed conservative cysteine substitutions in Aβ aiming at accelerating and stabilizing assembly of Aβ dimers by an intermolecular disulfide bond without changing its folding. Molecular dynamics simulations suggested that mutants AβS8C and AβM35C exhibited structural properties similar to those of Aβ wildtype dimers. Full length, mutant APP was stably expressed in transfected cell lines to study assembly of Aβ oligomers in the physiological, secretory pathway and to avoid artifacts resulting from simultaneous in vitro oxidation and aggregation. Biochemical and neurophysiological analysis of supernatants indicated that AβS8C generated an exclusive, homogeneous, and neurotoxic dimer, whereas AβM35C assembled into dimers, tetramers, and higher oligomers. Thus, molecular engineering enabled generation of bioactive, homogeneous, and correctly processed Aβ dimers in vivo.
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