Malarial proteases and host cell egress: an 'emerging' cascade.

Malarial proteases and host cell egress: an 'emerging' cascade.
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DOI:
10.1111/j.1462-5822.2008.01176.x
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发表时间:
2008-10
影响因子:
3.4
通讯作者:
Blackman, Michael J.
Blackman, Michael J.
中科院分区:
生物学2区
文献类型:
--
作者:
Blackman, Michael J.

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疟疾是地球仪大片地区的祸害,强调需要继续努力,更好地了解其病原体的生物学。像所有顶复门的病原体一样,疟原虫的部分生命是在宿主细胞或包囊内度过的。它最终需要逃离(出口)这个保护环境,以通过其生命周期的进展。疟原虫血液期裂殖子、肝脏期裂殖子和蚊子中肠子孢子的排出依赖于蛋白酶活性,因此所涉及的酶具有作为抗疟药物靶标的潜力。这篇评论探讨寄生虫蛋白酶在出口的作用,根据目前的知识的机制的过程。与排泄有关的蛋白酶包括降解细胞因子的疟疾蛋白酶falcipain-2和plasmepsin II,加上一个被称为SERA的推定木瓜蛋白酶样蛋白酶家族。最近的发现表明,SERA蛋白酶的激活可能是由一种称为SUB1的枯草杆菌蛋白酶样丝氨酸蛋白酶的调节分泌触发的。这些发现的背景下,针对寄生虫的生命周期的这一阶段的新的化疗药物的发展潜力进行了讨论。
Malaria is a scourge of large swathes of the globe, stressing the need for a continuing effort to better understand the biology of its aetiological agent. Like all pathogens of the phylum Apicomplexa, the malaria parasite spends part of its life inside a host cell or cyst. It eventually needs to escape (egress) from this protective environment to progress through its life cycle. Egress of Plasmodium blood-stage merozoites, liver-stage merozoites and mosquito midgut sporozoites relies on protease activity, so the enzymes involved have potential as antimalarial drug targets. This review examines the role of parasite proteases in egress, in the light of current knowledge of the mechanics of the process. Proteases implicated in egress include the cytoskeleton-degrading malarial proteases falcipain-2 and plasmepsin II, plus a family of putative papain-like proteases called SERA. Recent revelations have shown that activation of the SERA proteases may be triggered by regulated secretion of a subtilisin-like serine protease called SUB1. These findings are discussed in the context of the potential for development of new chemotherapeutics targeting this stage in the parasite's life cycle.
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