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Title: | Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance |
Author: | Colini Baldeschi, Arianna Zattoni, Marco Vanni, Silvia Nikolic, Lea Ferracin, Chiara La Sala, Giuseppina Summa, Maria Bertorelli, Rosalia Bertozzi, Sine Mandrup Giachin, Gabriele Carloni, Paolo Bolognesi, Maria Laura De Vivo, Marco Legname, Giuseppe |
Keywords: | Malalties per prions Metabolisme Prions Prion diseases Metabolism Prions |
Issue Date: | 30-Jun-2022 |
Publisher: | American Chemical Society (ACS) |
Abstract: | Prion diseases are a group of neurodegenerative disorders characterized by the accumulation of misfolded prion protein (called PrPSc). Although conversion of the cellular prion protein (PrPC) to PrPSc is still not completely understood, most of the therapies developed until now are based on blocking this process. Here, we propose a new drug strategy aimed at clearing prions without any direct interaction with neither PrPC nor PrPSc. Starting from the recent discovery of SERPINA3/SerpinA3n upregulation during prion diseases, we have identified a small molecule, named compound 5 (ARN1468), inhibiting the function of these serpins and effectively reducing prion load in chronically infected cells. Although the low bioavailability of this compound does not allow in vivo studies in prion-infected mice, our strategy emerges as a novel and effective approach to the treatment of prion disease. |
Note: | Reproducció del document publicat a: https://doi.org/10.1021/acs.jmedchem.2c00205 |
It is part of: | Journal of Medicinal Chemistry, 2022, vol. 65, num. 13, p. 8998-9010 |
URI: | http://hdl.handle.net/2445/188742 |
Related resource: | https://doi.org/10.1021/acs.jmedchem.2c00205 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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