Probing Neuroserpin Polymerization and Interaction with Amyloid-β Peptides Using Single Molecule Fluorescence

Probing protein-chaperone interactions with single-molecule fluorescence spectroscopy.

Effect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer’s Amyloid-β Peptides

The presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-β (Aβ), the peptide implicated in Alzheimer's disease (AD). The mechanism of why copper and zinc accelerate Aβ aggregation is poorly understood. In this work, we use single molecule force spectroscopy (SMFS) to probe ...

Single Molecule Characterization of the Interactions between Amyloid-β Peptides and the Membranes of Hippocampal Cells

Oligomers of the 40 and 42 residue amyloid-β peptides (Aβ40 and Aβ42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer's disease. However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells. In this work, we use single-molecule imaging techniques to examine the initial inter...

Single molecule probing by fluorescence and force detection.

The field of single molecule biophysics has rapidly grown in diverse directions. Enabled by improved microscopes and cameras, the temporal and spatial resolution of molecular detection has reached sub-nanometer and microsecond levels. An exciting new trend involves developing combination of fluorescence and force microscopy. Such tools allow for maneuvering and capturing extremely fine movement...

Interaction of Alzheimer's β-amyloid peptides with cholesterol: mechanistic insights into amyloid pore formation.

Brain cholesterol plays a critical role in Alzheimer's disease and other neurodegenerative diseases. The molecular mechanisms linking cholesterol to neurotoxicity have remained elusive for a long time, but recent data have allowed the identification of functional cholesterol-binding domains in several amyloidogenic proteins involved in neurodegenerative diseases, including Alzheimer's disease. ...