Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State 220005, Nigeria.
Center of Infectious Diseases, Parasitology, University of Heidelberg Medical School, INF324, 69120 Heidelberg, Germany.
Biomolecules. 2019 Jul 23;9(7):295. doi: 10.3390/biom9070295.
The survival of the human malaria parasite under the physiologically distinct environments associated with their development in the cold-blooded invertebrate mosquito vectors and the warm-blooded vertebrate human host requires a genome that caters to adaptability. To this end, a robust stress response system coupled to an efficient protein quality control system are essential features of the parasite. Heat shock proteins constitute the main molecular chaperone system of the cell, accounting for approximately two percent of the malaria genome. Some heat shock proteins of parasites constitute a large part (5%) of the 'exportome' (parasite proteins that are exported to the infected host erythrocyte) that modify the host cell, promoting its cyto-adherence. In light of their importance in protein folding and refolding, and thus the survival of the parasite, heat shock proteins of have been a major subject of study. Emerging evidence points to their role not only being cyto-protection of the parasite, as they are also implicated in regulating parasite virulence. In undertaking their roles, heat shock proteins operate in networks that involve not only partners of parasite origin, but also potentially functionally associate with human proteins to facilitate parasite survival and pathogenicity. This review seeks to highlight these interplays and their roles in parasite pathogenicity. We further discuss the prospects of targeting the parasite heat shock protein network towards the developments of alternative antimalarial chemotherapies.
人类疟原虫在冷血无脊椎蚊子媒介和温血脊椎动物人类宿主中发育所涉及的生理上不同的环境中生存，需要一个适应能力强的基因组。为此，一个强大的应激反应系统与高效的蛋白质质量控制系统是寄生虫的重要特征。热休克蛋白构成了细胞的主要分子伴侣系统，占疟原虫基因组的大约 2%。寄生虫的一些热休克蛋白构成了“外显子组”（寄生虫蛋白被输出到感染的宿主红细胞）的很大一部分（5%），改变了宿主细胞，促进其细胞附着。鉴于它们在蛋白质折叠和重折叠中的重要性，以及寄生虫的生存，热休克蛋白已成为主要的研究课题。新出现的证据表明，它们的作用不仅是对寄生虫的细胞保护，还涉及调节寄生虫的毒力。在发挥作用时，热休克蛋白在网络中运作，不仅涉及寄生虫来源的伙伴，还可能与人类蛋白在功能上有联系，以促进寄生虫的生存和致病性。本综述旨在强调这些相互作用及其在寄生虫致病性中的作用。我们还讨论了针对寄生虫热休克蛋白网络开发替代抗疟化疗药物的前景。
