Hauptseite > Publikationsdatenbank > Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance > print

001     909796
005     20240625095128.0
024 7 _ |a 10.1021/acs.jmedchem.2c00205
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024 7 _ |a 0095-9065
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037 _ _ |a FZJ-2022-03421
082 _ _ |a 610
100 1 _ |a Colini Baldeschi, Arianna
|0 0000-0002-8638-3705
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245 _ _ |a Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance
260 _ _ |a Washington, DC
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520 _ _ |a 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.
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700 1 _ |a Zattoni, Marco
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700 1 _ |a Vanni, Silvia
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700 1 _ |a Nikolic, Lea
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700 1 _ |a Ferracin, Chiara
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700 1 _ |a La Sala, Giuseppina
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700 1 _ |a Summa, Maria
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700 1 _ |a Bertorelli, Rosalia
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700 1 _ |a Bertozzi, Sine Mandrup
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700 1 _ |a Giachin, Gabriele
|0 0000-0001-7550-0307
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700 1 _ |a Carloni, Paolo
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700 1 _ |a Bolognesi, Maria Laura
|0 0000-0002-1289-5361
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700 1 _ |a De Vivo, Marco
|0 P:(DE-Juel1)167585
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700 1 _ |a Legname, Giuseppe
|0 0000-0003-0716-4393
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773 _ _ |a 10.1021/acs.jmedchem.2c00205
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|t Journal of medicinal chemistry
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