Artículo

Fauerbach, J.A.; Yushchenko, D.A.; Shahmoradian, S.H.; Chiu, W.; Jovin, T.M.; Jares-Erijman, E.A. "Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation" (2012) Biophysical Journal. 102(5):1127-1136
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Abstract:

The aggregation of α-synuclein is associated with progression of Parkinson's disease. We have identified submicrometer supramolecular structures that mediate the early stages of the overall mechanism. The sequence of structural transformations between metastable intermediates were captured and characterized by atomic force microscopy guided by a fluorescent probe sensitive to preamyloid species. A novel ∼0.3-0.6 μm molecular assembly, denoted the acuna, nucleates, expands, and liberates fibers with distinctive segmentation and a filamentous fuzzy fringe. These fuzzy fibers serve as precursors of mature amyloid fibrils. Cryo-electron tomography resolved the acuna inner structure as a scaffold of highly condensed colloidal masses interlinked by thin beaded threads, which were perceived as fuzziness by atomic force microscopy. On the basis of the combined data, we propose a sequential mechanism comprising molecular, colloidal, and fibrillar stages linked by reactions with disparate temperature dependencies and distinct supramolecular forms. We anticipate novel diagnostic and therapeutic approaches to Parkinson's and related neurodegenerative diseases based on these new insights into the aggregation mechanism of α-synuclein and intermediates, some of which may act to cause and/or reinforce neurotoxicity. © 2012 Biophysical Society.

Registro:

Documento: Artículo
Título:Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation
Autor:Fauerbach, J.A.; Yushchenko, D.A.; Shahmoradian, S.H.; Chiu, W.; Jovin, T.M.; Jares-Erijman, E.A.
Filiación:Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States
Laboratorio Max Planck de Dinámica Celular (UBA), Buenos Aires, Argentina
Palabras clave:alpha synuclein; proton; article; atomic force microscopy; chemical structure; chemistry; cryoelectron microscopy; protein multimerization; protein secondary structure; time; alpha-Synuclein; Cryoelectron Microscopy; Microscopy, Atomic Force; Models, Molecular; Protein Multimerization; Protein Structure, Secondary; Protons; Time Factors
Año:2012
Volumen:102
Número:5
Página de inicio:1127
Página de fin:1136
DOI: http://dx.doi.org/10.1016/j.bpj.2012.01.051
Título revista:Biophysical Journal
Título revista abreviado:Biophys. J.
ISSN:00063495
CODEN:BIOJA
CAS:alpha synuclein, 154040-18-3; proton, 12408-02-5, 12586-59-3; Protons; alpha-Synuclein
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v102_n5_p1127_Fauerbach

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Citas:

---------- APA ----------
Fauerbach, J.A., Yushchenko, D.A., Shahmoradian, S.H., Chiu, W., Jovin, T.M. & Jares-Erijman, E.A. (2012) . Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation. Biophysical Journal, 102(5), 1127-1136.
http://dx.doi.org/10.1016/j.bpj.2012.01.051
---------- CHICAGO ----------
Fauerbach, J.A., Yushchenko, D.A., Shahmoradian, S.H., Chiu, W., Jovin, T.M., Jares-Erijman, E.A. "Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation" . Biophysical Journal 102, no. 5 (2012) : 1127-1136.
http://dx.doi.org/10.1016/j.bpj.2012.01.051
---------- MLA ----------
Fauerbach, J.A., Yushchenko, D.A., Shahmoradian, S.H., Chiu, W., Jovin, T.M., Jares-Erijman, E.A. "Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation" . Biophysical Journal, vol. 102, no. 5, 2012, pp. 1127-1136.
http://dx.doi.org/10.1016/j.bpj.2012.01.051
---------- VANCOUVER ----------
Fauerbach, J.A., Yushchenko, D.A., Shahmoradian, S.H., Chiu, W., Jovin, T.M., Jares-Erijman, E.A. Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation. Biophys. J. 2012;102(5):1127-1136.
http://dx.doi.org/10.1016/j.bpj.2012.01.051