Capturing Aβ42 aggregation in the cell

Abstract

Novel imaging techniques with ever-increasing resolution are invaluable tools for the study of protein deposition, as they allow the self-assembly of proteins to be directly investigated in living cells. For the first time, the acceleration in Aβ42 aggregation induced by the Arctic mutation was monitored in cells, revealing a number of distinct morphologies that form sequentially. This approach will help discriminate the impacts of mutations on amyloid protein processing, Aβ aggregation propensity, and other mechanistic outcomes.

Amyloid self‐assembling peptides: Potential applications in nanovaccine engineering and biosensing

“…This is associated, in part, with the lack of precise mechanistic details of amyloid assembly that still remains the matter of active research . Amyloidogenic proteins and peptides can be divided into two different structural classes: those that are intrinsically (or partially) disordered in their native state and those that show a well‐defined tertiary structure in their monomeric soluble state . Generally, for natively folded polypeptides, including globular proteins, amyloid formation is initiated by partial unfolding/misfolding, favoring self‐recognition through interactions between aberrantly exposed hydrophobic domains .…”

“…Similarly, it was reported that peptide (neuro)hormones such as prolactin, oxytocin, and adrenocorticotropic hormone, are stored in secretory granules as amyloid‐like structures and that physiological amyloidogenesis enables cells to store proteins in a dormant state . Furthermore, recent advances in the molecular comprehension of protein misfolding diseases have proposed that the amyloid fibrils could play a protective role by sequestering misfolded proteins and/or toxic oligomers . Accordingly, the amyloid state appears as a protein quaternary conformation that could have essential biological functions.…”

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

“…Importantly, the molecular events leading to the formation of these species are supposed to appear 10–20 years before the symptoms become evident . Studies aimed at unraveling the relationship between structure and neurotoxicity of misfolded oligomers are thus pivotal in gaining insights into the pathological process, as well as in designing novel diagnostic and therapeutic strategies tuned toward the earliest and presymptomatic stages of the disease …”

Length‐Dependent Manifestation of Vibration Modes Regulates a Specific Intermediate Morphology of Aβ17‐42 in Different Environments

“…It is believed that aggregates of β‐amyloid (Aβ) peptide, the primary component of extracellular deposits, possess toxic characteristics in the brains of AD patients . Many studies have examined the structural characteristics of Aβ responsible for toxicity to further understand the pathological mechanisms . Aβ40 and Aβ42 are two common Aβ isoforms that are generated by improper differential C‐terminal cleavage of amyloid precursor proteins by β‐ and γ‐secretases.…”

“…In aqueous solutions or membranes, Aβ oligomers possess polymorphic structural characteristics depending on various environmental conditions, such as ionic concentrations, pH, and thermal fluctuations . It is known that formation of Aβ oligomers and their toxicities are altered based on their conformations ,,. The typical Aβ oligomeric conformations can be classified as fibrillar‐protofibril,,, spherical, and annular‐protofibril ,.…”