Fluorescent Markers for Amyloid‐β Detection: Computational Insights

Peccati, Francesca; Pantaleone, Stefano; Solans‐Monfort, Xavier; Sodupe, Mariona

doi:10.1002/ijch.201600114

Cited by 4 publications

(2 citation statements)

References 92 publications

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“…Many other fluorogenic dyes that bind amyloid also exist, some with desirable spectral properties. Examples include NIAD-4 [181] that has an enhanced Stokes shift [163,[182][183][184][185][186], and others that excite and emit towards the (near infra)red end of the spectrum (e.g. [184,[187][188][189][190]).…”

Section: Amyloid Detection With Thioflavin T and Other Stainsmentioning

confidence: 99%

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Kell,

Pretorius

2024

Preprint

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In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena occur in blood from individuals with circulating inflammatory molecules (also those originating from viruses and bacteria). In the presence of inflammagens, pathological clotting can occur, that results in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We provide evidence against a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant overlap with the normal plasma proteome and no correlation between plasma protein abundance and presence in microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand Factor are well represented. Using bioinformatic tools including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders.

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Section: Amyloid Detection With Thioflavin T and Other Stainsmentioning

confidence: 99%

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Kell,

Pretorius

2024

Preprint

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“…Since protein aggregates is a key event in Amyloidosis, therapeutic strategies are focused on the search for compounds able to interfere with this process, in particular by suppressing the formation or destruction of the toxic aggregate. Currently available in vitro [4] and in vivo [5] screening systems is based on production of amyloid proteins/peptides by solid phase peptide synthesis (SPPS) or recombinant DNA technique and utilize Thioflavin T (ThT), Thiophenes and Bodipy [6,7] based fluorescent probes to examine the presence or the degree of aggregation. Moreover, cell based biosensor has also been used for screening of amyloid disrupting molecules [8,9].…”

Section: Introductionmentioning

confidence: 99%

Diphenylalanin nanofibers-inspired synthesis of fluorescent gold nanoclusters for screening of anti-amyloid drugs

Zohrabi¹,

Amiri‐Sadeghan²,

Ganjali³

et al. 2020

Methods Appl. Fluoresc.

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Protein misfolding and aggregation into amyloid structures is linked with a number of pathophysiological disorders. In the past decade, significant progresses have been made in the drug discovery strategies against toxic aggregates. Although lack of specificity and high sensitivity for in vitro screening system still seen. Here we demonstrate a new targeting probe based on FF diphenylalanine peptide -protected gold nanoclusters (FF AuNCs). Diphenylalanine peptide has previously been shown to self-assemble into well-ordered fiber like the fibers that are observed in amyloid aggregates. We used of the self-assembly properties along with the ability of FF dipeptide in reduction of gold ions for synthesis of novel Au nanoclusters. We used FF AuNCs for monitoring of effectiveness of anti-amyloid drugs. Fluorescence was considerably diminished when drugs at different concentrations added, due to destruction of the amyloid fibers. Furthermore, the analysis of several components demonstrates significant selectivity against the amyloid disrupting molecules. Prepared FF AuNCs will gain possible strategy for in vitro screening of amyloid disrupting molecules.

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