Nanoscale Discrimination between Toxic and Nontoxic Protein Misfolded Oligomers with Tip‐Enhanced Raman Spectroscopy

Highly toxic protein misfolded oligomers associated with neurological disorders such as Alzheimer's and Parkinson's diseases are nowadays considered primarily responsible for promoting synaptic failure and neuronal death. Unraveling the relationship between structure and neurotoxicity of p...

Full description

Saved in:
Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2018-09, Vol.14 (36), p.e1800890-n/a
Main Authors: D'Andrea, Cristiano, Foti, Antonino, Cottat, Maximilien, Banchelli, Martina, Capitini, Claudia, Barreca, Francesco, Canale, Claudio, Angelis, Marella, Relini, Annalisa, Maragò, Onofrio M., Pini, Roberto, Chiti, Fabrizio, Gucciardi, Pietro G., Matteini, Paolo
Format: Article
Language:English
Subjects:
Alzheimer's disease
amyloid
biomolecules
Diagnostic systems
nanoscale
Nanotechnology
Oligomers
Proteins
Raman spectroscopy
Residues
Spatial resolution
Spectrum analysis
TERS
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Highly toxic protein misfolded oligomers associated with neurological disorders such as Alzheimer's and Parkinson's diseases are nowadays considered primarily responsible for promoting synaptic failure and neuronal death. Unraveling the relationship between structure and neurotoxicity of protein oligomers appears pivotal in understanding the causes of the pathological process, as well as in designing novel diagnostic and therapeutic strategies tuned toward the earliest and presymptomatic stages of the disease. Here, it is benefited from tip‐enhanced Raman spectroscopy (TERS) as a surface‐sensitive tool with spatial resolution on the nanoscale, to inspect the spatial organization and surface character of individual protein oligomers from two samples formed by the same polypeptide sequence and different toxicity levels. TERS provides direct assignment of specific amino acid residues that are exposed to a large extent on the surface of toxic species and buried in nontoxic oligomers. These residues, thanks to their outward disposition, might represent structural factors driving the pathogenic behavior exhibited by protein misfolded oligomers, including affecting cell membrane integrity and specific signaling pathways in neurodegenerative conditions. Tip‐enhanced Raman spectroscopy is exploited to unravel chemostructural differences between two protein misfolded oligomers with the same polypeptide sequence and different toxicity levels. Compelling evidence of the presence of peculiar determinants in the case of toxic oligomers is provided, which sheds new light on the mechanism by which they cause cellular impairment in neurodegenerative conditions.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.201800890