Počet záznamů: 1
Validation of Babesia proteasome as a drug target
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SYSNO ASEP 0498709 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Validation of Babesia proteasome as a drug target Tvůrce(i) Jalovecká, Marie (BC-A) RID
Hartmann, David (BC-A) ORCID, RID
Miyamoto, Y. (GB)
Eckmann, L. (US)
Hajdušek, Ondřej (BC-A) RID, ORCID
O'Donoghue, A.J. (US)
Sojka, Daniel (BC-A) RID, ORCIDCelkový počet autorů 7 Zdroj.dok. International Journal for Parasitology-Drugs and Drug Resistance . - : Elsevier - ISSN 2211-3207
Roč. 8, č. 3 (2018), s. 394-402Poč.str. 9 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Babesia ; Carfilzomib ; Cytotoxicity ; Epoxyketone ; Proteasome Vědní obor RIV GJ - Choroby a škůdci zvířat, veterinární medicína Obor OECD Veterinary science CEP GA17-14631S GA ČR - Grantová agentura ČR GA17-27386S GA ČR - Grantová agentura ČR Institucionální podpora BC-A - RVO:60077344 UT WOS 000452063600005 EID SCOPUS 85051269921 DOI 10.1016/j.ijpddr.2018.08.001 Anotace Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia. Testing the compounds against Babesia divergens ex vivo revealed suppressive effects on parasite growth with activity that was higher than the cytotoxic effects on a non-transformed mouse macrophage cell line. Furthermore, we showed that the most-effective compound, carfilzomib, significantly reduces parasite multiplication in a Babesia microti infected mouse model without noticeable adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and in vivo decrease in proteasome activity and accumulation of polyubiquitinated proteins compared to untreated control. Overall, our results demonstrate that the Babesia proteasome is a valid target for drug development and warrants the design of potent and selective B. divergens proteasome inhibitors for the treatment of babesiosis. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2019
Počet záznamů: 1