A Hybrid Structural Method for Investigating Low Molecular Weight Oligomeric Structures of Amyloid Beta. (13th September 2022)

• Record Type: Journal Article
• Authors: Gupta, Sayan; Raskatov, Jevgenij A.; Ralston, Corie Y.
• Is Part Of: Chembiochem. Volume 23:Number 23(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-13
• Subjects: Alzheimer's disease therapeutics -- amyloid beta -- hybrid methods -- hydroxyl radical footprinting -- oligomeric structures; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200333
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Spurred in part by the failure of recent therapeutics targeting amyloid β plaques in Alzheimer's Disease (AD), attention is increasingly turning to the oligomeric forms of this peptide that form early in the aggregation process. However, while numerous amyloid β fibril structures have been characterized, primarily by NMR spectroscopy and cryo‐EM, obtaining structural information on the low molecular weight forms of amyloid β that presumably precede and/or seed fibril formation has proved challenging. These transient forms are heterogeneous, and depend heavily on experimental conditions such as buffer, temperature, concentration, and degree of quiescence during measurement. Here, we present the concept for a new approach to delineating structural features of early‐stage low molecular weight amyloid β oligomers, using a solvent accessibility assay in conjunction with simultaneous fluorescence measurements. Abstract : Concept for a new hybrid characterization assay : Inline fluorescence collection can be used immediately prior to X‐ray exposure to simultaneously characterize the evolution of residue‐specific interactions and the evolution of global conformation along the amyloid aggregation timeline.