TY  - JOUR
AU  - Colini Baldeschi, Arianna
AU  - Zattoni, Marco
AU  - Vanni, Silvia
AU  - Nikolic, Lea
AU  - Ferracin, Chiara
AU  - La Sala, Giuseppina
AU  - Summa, Maria
AU  - Bertorelli, Rosalia
AU  - Bertozzi, Sine Mandrup
AU  - Giachin, Gabriele
AU  - Carloni, Paolo
AU  - Bolognesi, Maria Laura
AU  - De Vivo, Marco
AU  - Legname, Giuseppe
TI  - Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance
JO  - Journal of medicinal chemistry
VL  - 65
IS  - 13
SN  - 0022-2623
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2022-03421
SP  - 8998 - 9010
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 35771181
UR  - <Go to ISI:>//WOS:000836282300001
DO  - DOI:10.1021/acs.jmedchem.2c00205
UR  - https://juser.fz-juelich.de/record/909796
ER  -