TY  - JOUR
A1  - Makoah Nigel, Animake
A1  - Arndt, Hans-Dieter
A1  - Pradel, Gabriele
T1  - The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention?
JF  - International Journal for Parasitology: Drugs and Drug Resistance
N2  - The ubiquitin/proteasome system serves as a regulated protein degradation pathway in eukaryotes, and is involved in many cellular processes featuring high protein turnover rates, such as cell cycle control, stress response and signal transduction. In malaria parasites, protein quality control is potentially important because of the high replication rate and the rapid transformations of the parasite during life cycle progression. The proteasome is the core of the degradation pathway, and is a major proteolytic complex responsible for the degradation and recycling of non-functional ubiquitinated proteins. Annotation of the genome for Plasmodium falciparum, the causative agent of malaria tropica, revealed proteins with similarity to human 26S proteasome subunits. In addition, a bacterial ClpQ/hslV threonine peptidase-like protein was identified. In recent years several independent studies indicated an essential function of the parasite proteasome for the liver, blood and transmission stages. In this review, we compile evidence for protein recycling in Plasmodium parasites and discuss the role of the 26S proteasome as a prospective multi-stage target for antimalarial drug discovery programs.
KW  - plasmodium falciparum
KW  - proteasome
KW  - ubiquitin
KW  - inhibitor
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137777
VL  - 2
ER  - 
TY  - JOUR
A1  - Röhrich, Christian Rene
A1  - Ngwa, Che Julius
A1  - Wiesner, Jochen
A1  - Schmidtberg, Henrike
A1  - Degenkolb, Thomas
A1  - Kollewe, Christian
A1  - Fischer, Rainer
A1  - Pradel, Gabriele
A1  - Vilcinskas, Andreas
T1  - Harmonine, a defence compound from the harlequin ladybird, inhibits mycobacterial growth and demonstrates multi-stage antimalarial activity
JF  - Biology Letters
N2  - The harlequin ladybird beetle Harmonia axyridis has been introduced in many countries as a biological control agent, but has become an invasive species threatening the biodiversity of native ladybirds. Its invasive success has been attributed to its vigorous resistance against diverse pathogens. This study demonstrates that harmonine ((17R,9Z)-1,17-diaminooctadec-9-ene), which is present in H. axyridis haemolymph, displays broad-spectrum antimicrobial activity that includes human pathogens. Antibacterial activity is most pronounced against fast-growing mycobacteria and Mycobacterium tuberculosis, and the growth of both chloroquine-sensitive and -resistant Plasmodium falciparum strains is inhibited. Harmonine displays gametocytocidal activity, and inhibits the exflagellation of microgametocytes and zygote formation. In an Anopheles stephensi mosquito feeding model, harmonine displays transmission-blocking activity.
KW  - insect immunity
KW  - antimicrobial activity
KW  - harmonine
KW  - harmonia axyridis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127079
VL  - 8
ER  -