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.
Cell Transplant. 2020 Jan-Dec;29:963689719884888. doi: 10.1177/0963689719884888.
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 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 , , and . 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.
疟原虫等顶复门寄生虫近一个世纪以来一直是研究人员面临的挑战。开发有效治疗方法和疫苗的主要挑战是寄生虫能够改变其细胞和分子组成，在宿主中形成细胞内和细胞外小生境。钙信号是疟原虫从受感染的红细胞中逸出、配子发生、蚊媒中合子的运动以及疟原虫子孢子侵入哺乳动物肝细胞的重要信使。钙依赖性蛋白激酶（CDPK）在寄生虫生命周期的各个阶段的钙信号中具有重要功能；因此，它们成为抗疟疾药物的有吸引力的靶点。在这里，我们通过强调宿主组织内发育进展的分子机制，总结了各种 CDPK 同工型在疟原虫生命周期中的功能。我们还讨论了抗疟药物的现状，例如针对寄生虫 CDPK 的特定碰撞激酶抑制剂 (BKI) 如何显示可降低 在 、 和 中的感染。我们建议将 BKI 与过氧化物桥青蒿素衍生物和 Ca(2+)-ATPase PfATP6 的抑制剂相结合，作为治疗疟疾的潜在靶点，应该进一步检查。
