Krishna Sanjeev, Woodrow Charles J, Staines Henry M, Haynes Richard K, Mercereau-Puijalon Odile
Centre for Infection, Division of Cellular and Molecular Medicine, St. George's, University of London SW17 0RE, UK.
Trends Mol Med. 2006 May;12(5):200-5. doi: 10.1016/j.molmed.2006.03.005. Epub 2006 Apr 17.
There are more than half a billion cases of malaria every year. Combinations of an artemisinin with other antimalarial drugs are now recommended treatments for Plasmodium falciparum malaria in most endemic areas. These treatment regimens act rapidly to relieve symptoms and effect cure. There is considerable controversy on how artemisinins work and over emerging indications of resistance to this class of antimalarial drugs. Several individual molecules have been proposed as targets for artemisinins, in addition to the idea that artemisinins might have many targets at the same time. Our suggestion that artemisinins inhibit the parasite-encoded sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) PfATP6 has gained support from recent observations that a polymorphism in the gene encoding PfATP6 is associated with in vitro resistance to artemether in field isolates of P. falciparum.
每年有超过5亿例疟疾病例。目前，在大多数疟疾流行地区，青蒿素与其他抗疟药物的联合使用是治疗恶性疟原虫疟疾的推荐疗法。这些治疗方案能迅速缓解症状并实现治愈。关于青蒿素的作用机制以及这类抗疟药物新出现的耐药迹象存在相当大的争议。除了青蒿素可能同时有多个靶点的观点外，还提出了几个单独的分子作为青蒿素的靶点。我们提出青蒿素抑制寄生虫编码的肌浆内质网Ca(2+) - ATP酶（SERCA）PfATP6，这一观点得到了最近一些观察结果的支持，即编码PfATP6的基因中的多态性与恶性疟原虫野外分离株对蒿甲醚的体外耐药性有关。
