Nanostructural Differentiation and Toxicity of Amyloid-β25-35 Aggregates Ensue from Distinct Secondary Conformation

• Published in: Scientific reports Vol. 8; no. 1; pp. 765 - 9
• Main Authors: Song, Yongxiu, Li, Ping, Liu, Lei, Bortolini, Christian, Dong, Mingdong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-01-2018; Nature Publishing Group
• Subjects: 14/19; 631/57; 639/638/440; 639/925/357/341; Aggregates; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - toxicity; Cell interactions; Cell Line; Cell Membrane - drug effects; Cell Membrane - physiology; Cell Survival - drug effects; Cytotoxicity; Disease; Fibrils; Humanities and Social Sciences; Humans; Molecular structure; Movement disorders; multidisciplinary; Neurodegenerative diseases; Neurons - drug effects; Neurons - physiology; Parkinson's disease; Pathogenesis; Peptides; Protein Aggregation, Pathological; Protein folding; Protein structure; Protein Structure, Secondary; Science; Science (multidisciplinary); Secondary structure; Structural analysis; Toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-19106-y

Amyloid nanostructures are originated from protein misfolding and aberrant aggregation, which is associated with the pathogenesis of many types of degenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease. The secondary conformation of peptides is of a fundamental importance for aggregation and toxicity of amyloid peptides. In this work, Aβ25-35, a fragment of amyloid β(1-42) (Aβ42), was selected to investigate the correlation between secondary structures and toxicity of amyloid fibrils. Furthermore, each aggregation assemblies show different cell membrane disruption and cytotoxicity. The structural analysis of amyloid aggregates originated from different secondary structure motifs is helpful to understand the mechanism of peptides/cell interactions in the pathogenesis of amyloid diseases.