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Abstract:

The deposition of fibrillar structures (amyloids) is characteristic of pathological conditions including Alzheimer's and Parkinson's diseases. The detection of protein deposits and the evaluation of their kinetics of aggregation are generally based on fluorescent probes such as thioflavin T and Congo red. In a search for improved fluorescence tools for studying amyloid formation, we explored the ability of N-arylaminonaphthalene sulfonate (NAS) derivatives to act as noncovalent probes of α-synuclein (AS) fibrillation, a process linked to Parkinson's disease and other neurodegenerative disorders. The compounds bound to fibrillar AS with micromolar Kds, and exhibited fluorescence enhancement, hyperchromism, and high anisotropy. We conclude that the probes experience a hydrophobic environment and/or restricted motion in a polar region. Time- and spectrally resolved emission intensity and anisotropy provided further information regarding structural features of the protein and the dynamics of solvent relaxation. The steady-state and time-resolved parameters changed during the course of aggregation. Compared with thioflavin T, NAS derivatives constitute more sensitive and versatile probes for AS aggregation, and in the case of bis-NAS detect oligomeric as well as fibrillar species. They can function in convenient, continuous assays, thereby providing useful tools for studying the mechanisms of amyloid formation and for high-throughput screening of factors inhibiting and/or reversing protein aggregation in neurodegenerative diseases. © 2008 by the Biophysical Society.

Registro:

Documento: Artículo
Título:Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein
Autor:Celej, M.S.; Jares-Erijman, E.A.; Jovin, T.M.
Filiación:Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Departamento de Química Orgánica, Facultad de Ciencias Exactas Y Naturales, CIHIDECAR-CONICET, Buenos Aires, Argentina
Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
Palabras clave:alpha synuclein; amyloid; arylsulfonic acid derivative; fluorescent dye; multiprotein complex; article; chemistry; methodology; spectrofluorometry; alpha-Synuclein; Amyloid; Arylsulfonates; Fluorescent Dyes; Multiprotein Complexes; Spectrometry, Fluorescence
Año:2008
Volumen:94
Número:12
Página de inicio:4867
Página de fin:4879
DOI: http://dx.doi.org/10.1529/biophysj.107.125211
Título revista:Biophysical Journal
Título revista abreviado:Biophys. J.
ISSN:00063495
CODEN:BIOJA
CAS:alpha synuclein, 154040-18-3; amyloid, 11061-24-8; alpha-Synuclein; Amyloid; Arylsulfonates; Fluorescent Dyes; Multiprotein Complexes
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00063495_v94_n12_p4867_Celej.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v94_n12_p4867_Celej

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Citas:

---------- APA ----------
Celej, M.S., Jares-Erijman, E.A. & Jovin, T.M. (2008) . Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein. Biophysical Journal, 94(12), 4867-4879.
http://dx.doi.org/10.1529/biophysj.107.125211
---------- CHICAGO ----------
Celej, M.S., Jares-Erijman, E.A., Jovin, T.M. "Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein" . Biophysical Journal 94, no. 12 (2008) : 4867-4879.
http://dx.doi.org/10.1529/biophysj.107.125211
---------- MLA ----------
Celej, M.S., Jares-Erijman, E.A., Jovin, T.M. "Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein" . Biophysical Journal, vol. 94, no. 12, 2008, pp. 4867-4879.
http://dx.doi.org/10.1529/biophysj.107.125211
---------- VANCOUVER ----------
Celej, M.S., Jares-Erijman, E.A., Jovin, T.M. Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of α-synuclein. Biophys. J. 2008;94(12):4867-4879.
http://dx.doi.org/10.1529/biophysj.107.125211