Nanoprobing of misfolding and interactions of amyloid β 42 protein

Nanomedicine : Nanotechnology, Biology, and Medicine
Bo-Hyun Kim, Yuri L Lyubchenko

Abstract

The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer's disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed. Despite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectrosco...Continue Reading

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Citations

Dec 18, 2014·Biophysical Journal·Yuliang Zhang, Yuri L Lyubchenko
May 29, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Tian QiuYan-Mei Li
Apr 23, 2015·Biophysical Journal·Zhengjian LvYuri L Lyubchenko
Aug 5, 2016·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Srabasti AcharyaLisa J Lapidus
Oct 8, 2016·Nanoscale·Yuliang ZhangYuri L Lyubchenko
Jun 19, 2019·Nanoscale·Sibaprasad Maity, Yuri L Lyubchenko
May 15, 2016·Biopolymers·Zhengjian LvYuri L Lyubchenko
May 12, 2020·Frontiers in Molecular Biosciences·Sibaprasad Maity, Yuri L Lyubchenko
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Nov 22, 2020·Biophysical Chemistry·Emma E CawoodSheena E Radford
Mar 20, 2015·Chemical Reviews·Jessica Nasica-LabouzePhilippe Derreumaux
Aug 11, 2017·Journal of Chemical Information and Modeling·Tingting ZhangJiajie Zhang

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