Calcium-dependent Protein Kinases in Malaria Parasite Development and Infection.

Autor: Ghartey-Kwansah G; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China.; Department of Biomedical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.; Authors contributed equally to this article., Yin Q; Clinical Center of National Institutes of Health, Bethesda, MD, USA.; Authors contributed equally to this article., Li Z; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China.; Ohio State University School of Medicine, Columbus, OH, USA.; Authors contributed equally to this article., Gumpper K; Ohio State University School of Medicine, Columbus, OH, USA.; Authors contributed equally to this article., Sun Y; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China., Yang R; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China., Wang D; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China., Jones O; University of Pennsylvania School of Medicine, Animal Center, Philadelphia, PA, USA., Zhou X; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China.; Ohio State University School of Medicine, Columbus, OH, USA., Wang L; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China.; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Bryant J; University of Maryland School of Medicine, Baltimore, MD, USA., Ma J; Ohio State University School of Medicine, Columbus, OH, USA., Boampong JN; Department of Biomedical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana., Xu X; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University College of Life Sciences, Xi'an, China.
Jazyk: angličtina
Zdroj: Cell transplantation [Cell Transplant] 2020 Jan-Dec; Vol. 29, pp. 963689719884888.
DOI: 10.1177/0963689719884888
Abstrakt: Apicomplexan parasites have challenged researchers for nearly a century. A major challenge to developing efficient treatments and vaccines is the parasite's ability to change its cellular and molecular makeup to develop intracellular and extracellular niches in its hosts. Ca 2+ signaling is an important messenger for the egress of the malaria parasite from the infected erythrocyte, gametogenesis, ookinete motility in the mosquito, and sporozoite invasion of mammalian hepatocytes. Calcium-dependent protein kinases (CDPKs) have crucial functions in calcium signaling at various stages of the parasite's life cycle; this therefore makes them attractive drug targets against malaria. Here, we summarize the functions of the various CDPK isoforms in relation to the malaria life cycle by emphasizing the molecular mechanism of developmental progression within host tissues. We also discuss the current development of anti-malarial drugs, such as how specific bumped kinase inhibitors (BKIs) for parasite CDPKs have been shown to reduce infection in Toxoplasma gondii , Cryptosporidium parvum , and Plasmodium falciparum . Our suggested combinations of BKIs, artemisinin derivatives with peroxide bridge, and inhibitors on the Ca(2+)-ATPase PfATP6 as a potential target should be inspected further as a treatment against malaria.
Databáze: MEDLINE