Disaggregation-induced fluorescence enhancement of NIAD-4 for the optical imaging of amyloid-β fibrils
dc.contributor.author
dc.date.accessioned
2015-11-09T13:03:13Z
dc.date.available
2015-11-09T13:03:13Z
dc.date.issued
2015-08-14
dc.identifier.issn
1463-9076
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dc.description.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
dc.description.sponsorship
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)
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application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry (RSC)
dc.relation
info:eu-repo/grantAgreement/MICINN//CTQ2011-26573/ES/MODELIZACION QUIMICO CUANTICA DE FOTOQUIMICA Y TRANSFERENCIA ELECTRONICA: SISTEMAS GRANDES, EFECTOS COLECTIVOS Y CONTROL OPTICO/
AGAUR/2014-2017/2014SGR1202
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Reproducció digital del document publicat a: http://dx.doi.org/10.1039/c5cp02728d
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© Physical Chemistry Chemical Physics, 2015, vol. 17, núm. 30. p. 19718-19725
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Articles publicats (D-Q)
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Tots els drets reservats
dc.subject
dc.title
Disaggregation-induced fluorescence enhancement of NIAD-4 for the optical imaging of amyloid-β fibrils
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/embargoedAccess
dc.embargo.terms
Cap
dc.date.embargoEndDate
info:eu-repo/date/embargoEnd/2026-01-01
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.contributor.funder
dc.relation.ProjectAcronym
dc.identifier.eissn
1463-9084