Journal Article

FZJ-2022-03421

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance

Colini Baldeschi, A. ; Zattoni, M. ; Vanni, S. ; Nikolic, L. ; Ferracin, C. ; La Sala, G. ; Summa, M. ; Bertorelli, R. ; Bertozzi, S. M. ; Giachin, G. ; Carloni, P.FZJ* ; Bolognesi, M. L. ; De Vivo, M. ; Legname, G. (Corresponding author)

2022
ACS Washington, DC

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/31888  doi:10.1021/acs.jmedchem.2c00205

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.

---

Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2022

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---