Nanoprobing of misfolding and interactions of amyloid ? 42 protein.

ABSTRACT: The assembly of amyloid ? (A?) 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 A?40 peptides, and these studies allowed us to shed new light on transiently existing A?40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of A?42 peptide, the most toxic A? alloform. The quantitative analysis of SMFS data demonstrated that A? 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 A?40 and A?42 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 ? 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.

SUBMITTER: Kim BH 

PROVIDER: S-EPMC4019693 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature