Tip‐Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ<sub>1<b>–</b>42</sub> Fibrils at the Nanometer Scale

Bonhommeau, Sébastien; Talaga, David; Hunel, Julien; Cullin, Christophe; Lecomte, Sophie

doi:10.1002/ange.201610399

Cited by 33 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The beta-hairpin content in the CHC–Cter region (residues 17–21 and 30–36) varies between 8% (OPLS-AA) and 13% (AMBER99sb-ildn), while it is between 1.5 (AMBERsb14) and 5% (CHARMM22*). These significant differences in the beta-hairpin population spanning 17–36 among the force fields are particularly important, because this region can contain: (i) aggressive FAD mutations (A21G, E22Q, E22G, D23N), 4 (ii) chemical modifications either preventing (phosphorylation of S26) 4 or accelerating (lactam bridge between D23 and K28) 4 amyloid formation, or modulating toxicity (replacement of G25–S26– N27 by an azobenzene photoswitch), 78 and (iii) mutations producing less toxic fibrils (L34T) 79 or oligomers (L34T, 80 and G33I 81 ).…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

2017

View full text Add to dashboard Cite

The dimer of the amyloid-β peptide Aβ of 42 residues is the smallest toxic species in Alzheimer’s disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn, and AMBERsb14 force fields with the TIP3P water model. On the basis of 144 µs replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties, and small-angle X-ray scattering profiles independent of the force field. There are, however, marked differences in secondary structure, with the AMBERsb14 and CHARMM22* ensembles overestimating the CD-derived helix content, and the OPLS-AA and AMBER99sb-ildn secondary structure contents in agreement with CD data. Also the intramolecular beta-hairpin content spanning residues 17–21 and 30–36 varies between 1.5% and 13%. Overall, there are significant differences in tertiary and quaternary conformations among all force fields, and the key finding, irrespective of the force field, is that the dimer is stabilized by nonspecific interactions, explaining therefore its possible transient binding to multiple cellular partners and, in part, its toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

2017

View full text Add to dashboard Cite

show abstract

“…Therefore, Raman spectroscopy has advantages for identification of protein conformation and has been successfully utilized to detect the structure changes occurring at all stages of the formation of insoluble and noncrystalline protein aggregates. [12,[31][32][33][34][35][36][37][38] Through analyzing the amide I, II, and III bands in deep ultraviolet Raman spectra, a disordered secondary structure (the so-called statistical coil) was verified to be initially formed, [36] followed by assembly to β-sheet-rich oligomers. Consequently, the oligomers aggregated in multiple assembly states forming a nucleus, so that a large number of nuclei ultimately rapidly propagated into filaments and fibrils.…”

Section: Introductionmentioning

confidence: 99%

Amyloid formation kinetics of hen egg white lysozyme under heat and acidic conditions revealed by Raman spectroscopy

Xing

Fan

Chen

et al. 2019

J Raman Spectroscopy

View full text Add to dashboard Cite

Amyloid fibrillation of proteins is a hallmark of neurodegenerative disease, accompanied by the formation of the organized cross‐β cores. This conformational transformation is considered to be related to the toxicity underlying the pathogenic mechanism. However, the exact conformational transformation kinetics of amyloid fibrillation are not fully understood. Herein, Raman spectroscopy was used to detect the transformation in the molecular structure of hen egg white lysozyme during amyloid formation under heat and acidic conditions (pH 2.0 and 65°C). The overall kinetics of the hen egg white lysozyme conformational change were investigated by analyzing five characteristic spectral fingerprints. The two N–Cα–C stretching bands at 899 and 935 cm−1 and the amide I band (at 1,640–1,680 cm−1) correlated to the lysozyme skeleton structure, whereas the band of the Phe amino acid group in side chains at 1,003 cm−1 and the two Trp residue bands at 760 and 1,340–1,360 cm−1 were associated with the tertiary structure. Based on these results, a four‐stage step‐by‐step transformation mechanism is first proposed to describe the exact kinetics of lysozyme amyloid fibrillation under heat and acidic conditions. This provides necessary information for physiologists to artificially control the amyloid formation of neurodegenerative disease patients.

show abstract

“…Aβ has been the subject of TERS studies for tracking the structural variations on a single insulin fibril, 9 to evaluate the nanoscale heterogeneity of individual amyloid fibrils polymorphs 10 as well as to discriminate toxic oligomers with ~30 nm spatial resolution. 11 In addition to TERS, surfaceenhanced Raman spectroscopy (SERS) has been exploited for Aβ detection using nanoshells and nanofluidics. 12,13 These individual pieces of information are very valuable to critically assess surface chemistry from different types of extracellular Aβ aggregations, albeit they have not yet been applied to probe the presence of Aβ aggregation in the vicinity of cellular structures.…”

Section: Introductionmentioning

confidence: 99%

Tip-enhanced Raman spectroscopy of amyloid β at neuronal spines

Tabatabaei

Caetano

Pashee

et al. 2017

Analyst

View full text Add to dashboard Cite

The early stages of Alzheimer's disease pathogenesis are thought to occur at the synapse level, since synapse loss can be directly correlated with memory dysfunction. Considerable evidence has suggested that amyloid beta (Aβ), a secreted proteolytic derivative of amyloid precursor protein, appears to be a critical factor in the early 'synaptic failure' that is observed in Alzheimer's disease pathogenesis. The identification of Aβ at neuronal spines with high spatial resolution and high surface specificity would facilitate unraveling the intricate effect of Aβ on synapse loss and its effect on neighboring neuronal connections. Here, tip-enhanced Raman spectroscopy was used to map the presence of Aβ aggregations in the vicinity of the spines exposed to Aβ preformed in vitro. Exposure to Aβ was of 1 and 6 hours. The intensity variation of selected vibrational modes of Aβ was mapped by TERS for different exposure times to Aβ. Of interest, we discuss the distinct contributions of the amide modes from Aβ that are enhanced by the TERS process and in particular the suppression of the amide I mode in the context of recently reported observations in the literature.

show abstract

Tip‐Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ_1–42 Fibrils at the Nanometer Scale

Cited by 33 publications

References 28 publications

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

Amyloid formation kinetics of hen egg white lysozyme under heat and acidic conditions revealed by Raman spectroscopy

Tip-enhanced Raman spectroscopy of amyloid β at neuronal spines

Contact Info

Product

Resources

About

Tip‐Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ1–42 Fibrils at the Nanometer Scale

Cited by 33 publications

References 28 publications

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

High-Resolution Structures of the Amyloid-β 1–42 Dimers from the Comparison of Four Atomistic Force Fields

Amyloid formation kinetics of hen egg white lysozyme under heat and acidic conditions revealed by Raman spectroscopy

Tip-enhanced Raman spectroscopy of amyloid β at neuronal spines

Contact Info

Product

Resources

About

Tip‐Enhanced Raman Spectroscopy to Distinguish Toxic Oligomers from Aβ_1–42 Fibrils at the Nanometer Scale