Direct Nanospectroscopic Verification of the Amyloid Aggregation Pathway

Lipiec, Ewelina; Pérez-Guaita, David; Kaderli, Janina; Wood, Bayden Robert; Zenobi, Renato

doi:10.1002/ange.201803234

Cited by 13 publications

(19 citation statements)

References 35 publications

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“…Amyloidogenic trajectories are those that result in the formation of amyloid fibrils from prion-like proteins. − We investigated the ability of a relatively novel class of CNMs, viz. CQDs, to interfere in the processes leading to the seeding of fibrils.…”

Section: Discussionmentioning

confidence: 99%

“…Prion-like proteins including amyloid beta (Aβ), tau, lysozyme, islet amyloid precursor protein (IAPP), α-synuclein, and polyQ mutant Huntingtin protein (mHTT) aggregate from their soluble, monomeric forms to generate increasingly complex structures that eventually result in the formation of insoluble fibrils. − The trajectory from the soluble monomer-to-insoluble fibril includes the formation of oligomeric and protofibrillar precursors relatively early on in the protein misfolding landscape. − The oligomers, which occur as dimers, tetramers, hexamers, and dodecamers are toxic in nature and propagate by a self-templating mechanism to form, the somewhat less toxic, protofibrils. The protofibrils then further elongate to form fibrils.…”

Section: Introductionmentioning

confidence: 99%

“…They include the thioflavin T (ThT) fluorescence assay (to detect mature fibrils) and the dynamic light scattering (DLS) technique to measure particle size, among others (Scheme ). ,− …”

Section: Introductionmentioning

confidence: 99%

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Carbon Quantum Dots for Treatment of Amyloid Disorders

Guerrero

Lopez-Velazquez

Ahlawat

et al. 2021

ACS Appl. Nano Mater.

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Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na−citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibrilforming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. A pulse-chase lysozyme fibrilforming assay developed to examine the impact of CQDs on the HEWL amyloid-fibril-forming trajectory used ThT fluorescence as a reporter of mature fibril presence. The results revealed that the Na−citrate-derived CQDs were able to intervene at multiple points along the fibril-forming trajectory by preventing the conversion of both monomeric and oligomeric HEWL intermediates into mature fibrils. In addition, and importantly, the carbon nano material (CNM) was able to dissolve oligomeric HEWL into monomeric HEWL and provoke the disaggregation of mature HEWL fibrils. These results suggest that Na−citrate CQD's intervene in amyloidogenesis by multiple mechanisms. The gathered data, coupled with cell-line results demonstrating the relatively low cytotoxicity of Na−citrate CQDs, suggest that this emerging CNM has the potential to intervene both prophylactically and therapeutically in protein misfolding diseases. The aforementioned findings are likely to enable Na−citrate CQDs to eventually transition to both cell-line and preclinical models of protein-misfolding-related disorders. Importantly, the study outcomes positions Na−citrate CQDs as an important class of chemical, nanotechnological, and biobased interventional tools in neuroscience.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carbon Quantum Dots for Treatment of Amyloid Disorders

Guerrero

Lopez-Velazquez

Ahlawat

et al. 2021

ACS Appl. Nano Mater.

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“…For clarity, TER marker bands related to the abnormal amyloid aggregation are presented in Table 6. One of the first neurodegenerative peptides characterized with TERS was β2-microglobulin [113]. Several polypeptides were intensively studied by the group of prof. Deckert from Jena University.…”

Section: Ters In Studies Of Abnormal Proteins/peptide Aggregationmentioning

confidence: 99%

Molecular Spectroscopic Markers of Abnormal Protein Aggregation

et al. 2020

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Abnormal protein aggregation has been intensively studied for over 40 years and broadly discussed in the literature due to its significant role in neurodegenerative diseases etiology. Structural reorganization and conformational changes of the secondary structure upon the aggregation determine aggregation pathways and cytotoxicity of the aggregates, and therefore, numerous analytical techniques are employed for a deep investigation into the secondary structure of abnormal protein aggregates. Molecular spectroscopies, including Raman and infrared ones, are routinely applied in such studies. Recently, the nanoscale spatial resolution of tip-enhanced Raman and infrared nanospectroscopies, as well as the high sensitivity of the surface-enhanced Raman spectroscopy, have brought new insights into our knowledge of abnormal protein aggregation. In this review, we order and summarize all nano- and micro-spectroscopic marker bands related to abnormal aggregation. Each part presents the physical principles of each particular spectroscopic technique listed above and a concise description of all spectral markers detected with these techniques in the spectra of neurodegenerative proteins and their model systems. Finally, a section concerning the application of multivariate data analysis for extraction of the spectral marker bands is included.

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“…8 AFM–TERS, on the other hand, is more versatile, since it is neither substrate-sensitive nor limited by the sample thickness and can thus be used for a much wider variety of applications, e.g., the characterization of biological membranes or dielectric materials. 9 Experiments were successfully performed on lipids, 10 DNA, 11 and proteins, 12 even in a liquid environment 13 using AFM–TERS. The heart of every AFM–TERS experiment is an enhancing plasmonic probe; commercially available AFM cantilevers, usually made of Si, need to be metalized to become suitable TERS probes.…”

Section: Introductionmentioning

confidence: 99%