Communications Biology (Jan 2021)
Pharmacological inactivation of the prion protein by targeting a folding intermediate
- Giovanni Spagnolli,
- Tania Massignan,
- Andrea Astolfi,
- Silvia Biggi,
- Marta Rigoli,
- Paolo Brunelli,
- Michela Libergoli,
- Alan Ianeselli,
- Simone Orioli,
- Alberto Boldrini,
- Luca Terruzzi,
- Valerio Bonaldo,
- Giulia Maietta,
- Nuria L. Lorenzo,
- Leticia C. Fernandez,
- Yaiza B. Codeseira,
- Laura Tosatto,
- Luise Linsenmeier,
- Beatrice Vignoli,
- Gianluca Petris,
- Dino Gasparotto,
- Maria Pennuto,
- Graziano Guella,
- Marco Canossa,
- Hermann C. Altmeppen,
- Graziano Lolli,
- Stefano Biressi,
- Manuel M. Pastor,
- Jesús R. Requena,
- Ines Mancini,
- Maria L. Barreca,
- Pietro Faccioli,
- Emiliano Biasini
Affiliations
- Giovanni Spagnolli
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Tania Massignan
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Andrea Astolfi
- Department of Pharmaceutical Sciences, University of Perugia
- Silvia Biggi
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Marta Rigoli
- Department of Physics, University of Trento, Povo
- Paolo Brunelli
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Michela Libergoli
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Alan Ianeselli
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Simone Orioli
- Department of Physics, University of Trento, Povo
- Alberto Boldrini
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Luca Terruzzi
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Valerio Bonaldo
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Giulia Maietta
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Nuria L. Lorenzo
- CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS
- Leticia C. Fernandez
- CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS
- Yaiza B. Codeseira
- CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS
- Laura Tosatto
- Institute of Biophysics, National Council of Research, 38123 Povo
- Luise Linsenmeier
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf
- Beatrice Vignoli
- Department of Physics, University of Trento, Povo
- Gianluca Petris
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Dino Gasparotto
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Maria Pennuto
- Department of Biomedical Sciences (DBS), University of Padova
- Graziano Guella
- Department of Physics, University of Trento, Povo
- Marco Canossa
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Hermann C. Altmeppen
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf
- Graziano Lolli
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Stefano Biressi
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Manuel M. Pastor
- RIAIDT, University of Santiago de Compostela-IDIS
- Jesús R. Requena
- CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS
- Ines Mancini
- Department of Physics, University of Trento, Povo
- Maria L. Barreca
- Department of Pharmaceutical Sciences, University of Perugia
- Pietro Faccioli
- Department of Physics, University of Trento, Povo
- Emiliano Biasini
- Department of Cellular, Computational and Integrative Biology, University of Trento
- DOI
- https://doi.org/10.1038/s42003-020-01585-x
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 16
Abstract
Spagnolli, Massignan, Astolfi et al. design a new drug discovery approach, termed Pharmacological Protein Inactivation by Folding Intermediate Targeting, in which folding intermediates of disease-causing proteins are targeted. They test it on the cellular prion protein, identifying ligands stabilizing a folding intermediate and consequently promoting its degradation by the cellular quality control machinery.