Počet záznamů: 1  

Validation of Babesia proteasome as a drug target

  1. 1.
    SYSNO ASEP0498709
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevValidation 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, ORCID
    Celkový počet autorů7
    Zdroj.dok.International Journal for Parasitology-Drugs and Drug Resistance . - : Elsevier - ISSN 2211-3207
    Roč. 8, č. 3 (2018), s. 394-402
    Poč.str.9 s.
    Forma vydáníTištěná - P
    Jazyk dok.eng - angličtina
    Země vyd.GB - Velká Británie
    Klíč. slovaBabesia ; Carfilzomib ; Cytotoxicity ; Epoxyketone ; Proteasome
    Vědní obor RIVGJ - Choroby a škůdci zvířat, veterinární medicína
    Obor OECDVeterinary science
    CEPGA17-14631S GA ČR - Grantová agentura ČR
    GA17-27386S GA ČR - Grantová agentura ČR
    Institucionální podporaBC-A - RVO:60077344
    UT WOS000452063600005
    EID SCOPUS85051269921
    DOI10.1016/j.ijpddr.2018.08.001
    AnotaceBabesiosis 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.
    PracovištěBiologické centrum (od r. 2006)
    KontaktDana Hypšová, eje@eje.cz, Tel.: 387 775 214
    Rok sběru2019
Počet záznamů: 1  

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