Compartir
Título
Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine
Autor(es)
Materia
Leishmaniosis
Molecular biology
Tratamiento
MItocondrias
Fecha de publicación
2017
Editor
Public Library of Science (New York)
Citación
Villa-Pulgarín, J.A., Gajate, C., Botet, J., Jiménez, A., Justies, N, Varela-M, R.E., et al. (2017) Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine. PLoS Negl Trop Dis 11(8): e0005805
Resumen
[EN]Leishmaniasis is a major health problem worldwide, and can result in loss of human life or a
lifelong stigma because of bodily scars. According to World Health Organization, leishmaniasis
is considered as an emerging and uncontrolled disease, and its current treatment is far
from ideal, with only a few drugs available that could lead to drug resistance or cause serious
side-effects. Here, we have found that mitochondria and raft-located FOF1-ATPase synthase
are efficient druggable targets, through which an ether lipid named edelfosine exerts its antileishmanial
action. Edelfosine effectively kills Leishmania spp. promastigotes and amastigotes.
Our experimental animal models demonstrate that oral administration of edelfosine exerts a
potent antileishmanial activity, while inhibits macrophage pro-inflammatory responses. Our
results show that both Leishmania and tumor cells share mitochondria and raft-located
FOF1-ATPase synthase as major druggable targets in leishmaniasis and cancer therapy. These
data, showing a potent antileishmanial activity of edelfosine and unveiling its mechanism of
action, together with the inhibition of the inflammatory responses elicited by macrophages,
suggest that the ether lipid edelfosine is a promising oral drug for leishmaniasis, and highlight
mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets for the
treatment of this disease.
URI
ISSN
1935-2727
DOI
10.1371/journal.pntd.0005805
Versión del editor
Colecciones