TY  - JOUR
AU  - Karagianni, Korina
AU  - Pettas, Spyros
AU  - Kanata, Eirini
AU  - Lioulia, Elisavet
AU  - Thune, Katrin
AU  - Schmitz, Matthias
AU  - Tsamesidis, Ioannis
AU  - Lymperaki, Evgenia
AU  - Xanthopoulos, Konstantinos
AU  - Sklaviadis, Theodoros
AU  - Dafou, Dimitra
TI  - Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases
JO  - Antioxidants
VL  - 11
IS  - 4
SN  - 2076-3921
CY  - Basel
PB  - MDPI
M1  - DZNE-2022-00464
SP  - 726
PY  - 2022
AB  - Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrPC) to the disease-associated (PrPSc). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have well-documented anti-oxidative and neuroprotective effects. Since oxidative stress plays an important role in the pathogenesis of prion diseases, we investigated the potential beneficial role of CA and CS in a cellular model of prion diseases (N2a22L cells) and in a cell-free prion amplification assay (RT-QuIC). The antioxidant effects of the compounds were confirmed when N2a22L were incubated with CA or CS. Furthermore, CA and CS reduced the accumulation of the disease-associated form of PrP, detected by Western Blotting, in N2a22L cells. This effect was validated in RT-QuIC assays, indicating that it is not associated with the antioxidant effects of CA and CS. Importantly, cell-free assays revealed that these natural products not only prevent the formation of PrP aggregates but can also disrupt already formed aggregates. Our results indicate that CA and CS have pleiotropic effects against prion diseases and could evolve into useful prophylactic and/or therapeutic agents against prion and other neurodegenerative diseases.
LB  - PUB:(DE-HGF)16
C6  - pmid:35453411
C2  - pmc:PMC9027925
DO  - DOI:10.3390/antiox11040726
UR  - https://pub.dzne.de/record/163725
ER  -