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顶质体驻留过程:利用寄生虫防护中的薄弱环节

Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Parasites.

作者信息

Mamudu Collins Ojonugwa, Tebamifor Mercy Eyitomi, Sule Mary Ohunene, Dokunmu Titilope Modupe, Ogunlana Olubanke Olujoke, Iheagwam Franklyn Nonso

机构信息

Department of Biochemistry, Covenant University, Ota, Nigeria.

Covenant Applied Informatics and Communication Africa Centre of Excellence, Ota, Nigeria.

出版信息

Adv Pharmacol Pharm Sci. 2024 May 10;2024:9940468. doi: 10.1155/2024/9940468. eCollection 2024.

Abstract

The discovery of a relict plastid, also known as an apicoplast (apicomplexan plastid), that houses housekeeping processes and metabolic pathways critical to parasites' survival has prompted increased research on identifying potent inhibitors that can impinge on apicoplast-localised processes. The apicoplast is absent in humans, yet it is proposed to originate from the eukaryote's secondary endosymbiosis of a primary symbiont. This symbiotic relationship provides a favourable microenvironment for metabolic processes such as haem biosynthesis, Fe-S cluster synthesis, isoprenoid biosynthesis, fatty acid synthesis, and housekeeping processes such as DNA replication, transcription, and translation, distinct from analogous mammalian processes. Recent advancements in comprehending the biology of the apicoplast reveal it as a vulnerable organelle for malaria parasites, offering numerous potential targets for effective antimalarial therapies. We provide an overview of the metabolic processes occurring in the apicoplast and discuss the organelle as a viable antimalarial target in light of current advances in drug discovery. We further highlighted the relevance of these metabolic processes to during the different stages of the lifecycle.

摘要

一种残留质体(也称为顶质体,即顶复门生物质体)的发现引发了对识别能够影响顶质体定位过程的有效抑制剂的更多研究。这种残留质体负责维持对寄生虫生存至关重要的管家过程和代谢途径。顶质体在人类中不存在,但据推测它起源于真核生物对一种初级共生体的二次内共生。这种共生关系为诸如血红素生物合成、铁硫簇合成、类异戊二烯生物合成、脂肪酸合成等代谢过程以及诸如DNA复制、转录和翻译等管家过程提供了一个有利的微环境,这些过程与类似的哺乳动物过程不同。在理解顶质体生物学方面的最新进展表明,它是疟原虫的一个易损细胞器,为有效的抗疟治疗提供了众多潜在靶点。我们概述了顶质体中发生的代谢过程,并根据药物发现的当前进展讨论了将该细胞器作为可行抗疟靶点的情况。我们还进一步强调了这些代谢过程在生命周期不同阶段的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f98/11101256/caa9f0604bb3/APS2024-9940468.001.jpg

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