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000909796 0247_ $$2doi$$a10.1021/acs.jmedchem.2c00205
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000909796 1001_ $$00000-0002-8638-3705$$aColini Baldeschi, Arianna$$b0
000909796 245__ $$aInnovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance
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000909796 520__ $$aPrion diseases are a group of neurodegenerative disorders characterized by the accumulation of misfolded prion protein (called PrPSc). Although conversion of the cellular prion protein (PrPC) to PrPSc is still not completely understood, most of the therapies developed until now are based on blocking this process. Here, we propose a new drug strategy aimed at clearing prions without any direct interaction with neither PrPC nor PrPSc. Starting from the recent discovery of SERPINA3/SerpinA3n upregulation during prion diseases, we have identified a small molecule, named compound 5 (ARN1468), inhibiting the function of these serpins and effectively reducing prion load in chronically infected cells. Although the low bioavailability of this compound does not allow in vivo studies in prion-infected mice, our strategy emerges as a novel and effective approach to the treatment of prion disease.
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000909796 7001_ $$0P:(DE-HGF)0$$aZattoni, Marco$$b1
000909796 7001_ $$0P:(DE-HGF)0$$aVanni, Silvia$$b2
000909796 7001_ $$0P:(DE-HGF)0$$aNikolic, Lea$$b3
000909796 7001_ $$0P:(DE-HGF)0$$aFerracin, Chiara$$b4
000909796 7001_ $$0P:(DE-HGF)0$$aLa Sala, Giuseppina$$b5
000909796 7001_ $$aSumma, Maria$$b6
000909796 7001_ $$aBertorelli, Rosalia$$b7
000909796 7001_ $$aBertozzi, Sine Mandrup$$b8
000909796 7001_ $$00000-0001-7550-0307$$aGiachin, Gabriele$$b9
000909796 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b10
000909796 7001_ $$00000-0002-1289-5361$$aBolognesi, Maria Laura$$b11
000909796 7001_ $$0P:(DE-Juel1)167585$$aDe Vivo, Marco$$b12
000909796 7001_ $$00000-0003-0716-4393$$aLegname, Giuseppe$$b13$$eCorresponding author
000909796 773__ $$0PERI:(DE-600)1491411-6$$a10.1021/acs.jmedchem.2c00205$$gVol. 65, no. 13, p. 8998 - 9010$$n13$$p8998 - 9010$$tJournal of medicinal chemistry$$v65$$x0022-2623$$y2022
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