title: Nanoprobing of misfolding and interactions of amyloid β 42 protein.
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.
  
  
  BACKGROUND
  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 spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
authors: Bo-Hyun
authors: BH
authors: Kim
authors: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA. Electronic address: ylyubchenko@unmc.edu.
authors: Yuri L
authors: YL
authors: Lyubchenko
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Amyloid beta; Contour length; Dimerization pathways; Misfolding; Single-molecule force spectroscopy