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Disaggregation-induced fluorescence enhancement of NIAD-4 for the optical imaging of amyloid-β fibrils

The main hallmark of Alzheimer’s disease is the deposition of amyloid-β (Aβ) aggregates in the brain. An early diagnosis of the disease requires a fast and accurate detection of such aggregates in vivo. NIAD-4 is one of the most promising in vivo markers developed due to its high emission at λ > 600 nm and its ability to rapidly cross the blood-brain barrier (BBB) and target Aβ deposits. Furthermore, it shows a dramatic fluorescence enhancement upon binding to amyloid fibrils, which is essential for attaining good imaging contrast. Aiming at establishing novel design concepts for the preparation of optimized optical probes, the current work rationalizes the excellent performance of NIAD-4 by using a pool of computational (TD-DFT and CASPT2 calculations, ab initio molecular dynamics and protein energy landscape exploration) and spectroscopic techniques. Unlike other markers operating as molecular rotors or polarity-sensitive dyes, we uncover herein that the high fluorescence imaging contrast observed upon NIAD-4 binding to amyloid fibrils results from reversible aggregation. NIAD-4 forms non-emissive assemblies in aqueous solution already at very low concentrations, which convert into the highly fluorescent monomeric species by diffusion into the hydrophobic voids of Aβ deposits. This result paves the way to exploit aggregation-induced processes as a new strategy towards advanced fluorescence markers for amyloid detection

The authors gratefully acknowledge financial support from MINECO (projects CTQ2012-30853, CTQ2011-26573 and CTQ2011-24847) and the Generalitat de Catalunya (projects 2014SGR-1202 and 2014SGR-482)

© Physical Chemistry Chemical Physics, 2015, vol. 17, núm. 30. p. 19718-19725

Royal Society of Chemistry (RSC)

Manager: Ministerio de Ciencia e Innovación (Espanya)
Generalitat de Catalunya. Agència de Gestió d’Ajuts Universitaris i de Recerca
Author: Peccati, Francesca
Hernando, Jordi
Blancafort San José, Lluís
Solans Monfort, Xavier
Sodupe Roure, Mariona
Date: 2015 August 14
Abstract: The main hallmark of Alzheimer’s disease is the deposition of amyloid-β (Aβ) aggregates in the brain. An early diagnosis of the disease requires a fast and accurate detection of such aggregates in vivo. NIAD-4 is one of the most promising in vivo markers developed due to its high emission at λ > 600 nm and its ability to rapidly cross the blood-brain barrier (BBB) and target Aβ deposits. Furthermore, it shows a dramatic fluorescence enhancement upon binding to amyloid fibrils, which is essential for attaining good imaging contrast. Aiming at establishing novel design concepts for the preparation of optimized optical probes, the current work rationalizes the excellent performance of NIAD-4 by using a pool of computational (TD-DFT and CASPT2 calculations, ab initio molecular dynamics and protein energy landscape exploration) and spectroscopic techniques. Unlike other markers operating as molecular rotors or polarity-sensitive dyes, we uncover herein that the high fluorescence imaging contrast observed upon NIAD-4 binding to amyloid fibrils results from reversible aggregation. NIAD-4 forms non-emissive assemblies in aqueous solution already at very low concentrations, which convert into the highly fluorescent monomeric species by diffusion into the hydrophobic voids of Aβ deposits. This result paves the way to exploit aggregation-induced processes as a new strategy towards advanced fluorescence markers for amyloid detection
The authors gratefully acknowledge financial support from MINECO (projects CTQ2012-30853, CTQ2011-26573 and CTQ2011-24847) and the Generalitat de Catalunya (projects 2014SGR-1202 and 2014SGR-482)
Format: application/pdf
ISSN: 1463-9076 (versió paper)
1463-9084 (versió electrònica)
Document access: http://hdl.handle.net/10256/11466
Language: eng
Publisher: Royal Society of Chemistry (RSC)
Collection: MICINN/PN 2012-2014/CTQ2011-26573
AGAUR/2014-2017/2014SGR1202
Reproducció digital del document publicat a: http://dx.doi.org/10.1039/c5cp02728d
Articles publicats (D-Q)
Is part of: © Physical Chemistry Chemical Physics, 2015, vol. 17, núm. 30. p. 19718-19725
Rights: Tots els drets reservats
Subject: Alzheimer, Malaltia d’
Alzheimer’s disease
Proteïnes -- Agregació
Protéines -- Agrégation
Title: Disaggregation-induced fluorescence enhancement of NIAD-4 for the optical imaging of amyloid-β fibrils
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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