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Open Access
Peer-reviewed
Research Article
Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson’s Disease
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Gergely Tóth ,
* E-mail: lisam@msg.ucsf.edu (LM); gt293@cam.ac.uk (GT); mv245@cam.ac.uk (MV); dale.schenk@prothena.com (DS); cmd44@cam.ac.uk (CMD)
Affiliations Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, Elan Pharmaceuticals, South San Francisco, California, United States of America
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Shyra J. Gardai,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Wagner Zago,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Carlos W. Bertoncini,
Affiliations Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, SEDIPFAR (Servicio De Descubrimiento, Diseño Y Desarrollo Pre-Clínico De Fármacos De La Argentina) drug discovery platform, Universidad Nacional de Rosario, Rosario, Argentina
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Nunilo Cremades,
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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Susan L. Roy,
Affiliation Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, United States of America
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Mitali A. Tambe,
Affiliation Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, United States of America
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Jean-Christophe Rochet,
Affiliation Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, United States of America
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Celine Galvagnion,
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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Gaia Skibinski,
Affiliations Gladstone Institute of Neurological Disease, San Francisco, California, United States of America, Taube-Koret Center for Neurodegenerative Disease Research, The Consortium for Frontotemporal Dementia Research, and The Hellman Family Foundation Program for Alzheimer’s Disease Research, San Francisco, California, United States of America
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Steven Finkbeiner,
Affiliations Gladstone Institute of Neurological Disease, San Francisco, California, United States of America, Taube-Koret Center for Neurodegenerative Disease Research, The Consortium for Frontotemporal Dementia Research, and The Hellman Family Foundation Program for Alzheimer’s Disease Research, San Francisco, California, United States of America, Departments of Neurology and Physiology, UCSF, San Francisco, California, United States of America
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Michael Bova,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Karin Regnstrom,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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San-San Chiou,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Jennifer Johnston,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Kari Callaway,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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John P. Anderson,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Michael F. Jobling,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Alexander K. Buell,
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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Ted A. Yednock,
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Tuomas P. J. Knowles,
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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Michele Vendruscolo ,
* E-mail: lisam@msg.ucsf.edu (LM); gt293@cam.ac.uk (GT); mv245@cam.ac.uk (MV); dale.schenk@prothena.com (DS); cmd44@cam.ac.uk (CMD)
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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John Christodoulou,
Affiliation Department of Structural & Molecular Biology, University College London, London, United Kingdom
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Christopher M. Dobson ,
* E-mail: lisam@msg.ucsf.edu (LM); gt293@cam.ac.uk (GT); mv245@cam.ac.uk (MV); dale.schenk@prothena.com (DS); cmd44@cam.ac.uk (CMD)
Affiliation Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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Dale Schenk ,
* E-mail: lisam@msg.ucsf.edu (LM); gt293@cam.ac.uk (GT); mv245@cam.ac.uk (MV); dale.schenk@prothena.com (DS); cmd44@cam.ac.uk (CMD)
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Lisa McConlogue
* E-mail: lisam@msg.ucsf.edu (LM); gt293@cam.ac.uk (GT); mv245@cam.ac.uk (MV); dale.schenk@prothena.com (DS); cmd44@cam.ac.uk (CMD)
Affiliation Elan Pharmaceuticals, South San Francisco, California, United States of America
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Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson’s Disease
- Gergely Tóth,
- Shyra J. Gardai,
- Wagner Zago,
- Carlos W. Bertoncini,
- Nunilo Cremades,
- Susan L. Roy,
- Mitali A. Tambe,
- Jean-Christophe Rochet,
- Celine Galvagnion,
- Gaia Skibinski

- Published: February 14, 2014
- https://doi.org/10.1371/journal.pone.0087133