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恶性疟原虫蛋白酶作为新的药物靶点,特别关注金属蛋白酶。

Plasmodium falciparum proteases as new drug targets with special focus on metalloproteases.

机构信息

Department of Biotechnology, National Institute of Technology, Arunachal Pradesh, India.

Department of Biotechnology, National Institute of Technology, Arunachal Pradesh, India.

出版信息

Mol Biochem Parasitol. 2024 Jun;258:111617. doi: 10.1016/j.molbiopara.2024.111617. Epub 2024 Mar 29.

Abstract

Malaria poses a significant global health threat particularly due to the prevalence of Plasmodium falciparum infection. With the emergence of parasite resistance to existing drugs including the recently discovered artemisinin, ongoing research seeks novel therapeutic avenues within the malaria parasite. Proteases are promising drug targets due to their essential roles in parasite biology, including hemoglobin digestion, merozoite invasion, and egress. While exploring the genomic landscape of Plasmodium falciparum, it has been revealed that there are 92 predicted proteases, with only approximately 14 of them having been characterized. These proteases are further distributed among 26 families grouped into five clans: aspartic proteases, cysteine proteases, metalloproteases, serine proteases, and threonine proteases. Focus on metalloprotease class shows further role in organelle processing for mitochondria and apicoplasts suggesting the potential of metalloproteases as viable drug targets. Holistic understanding of the parasite intricate life cycle and identification of potential drug targets are essential for developing effective therapeutic strategies against malaria and mitigating its devastating global impact.

摘要

疟疾是一个严重的全球健康威胁,特别是由于恶性疟原虫感染的流行。随着寄生虫对现有药物(包括最近发现的青蒿素)的耐药性的出现,目前正在疟疾寄生虫内寻找新的治疗方法。蛋白酶是有前途的药物靶点,因为它们在寄生虫生物学中起着至关重要的作用,包括血红蛋白消化、裂殖体入侵和逸出。在探索恶性疟原虫的基因组景观时,已经揭示出有 92 种预测的蛋白酶,其中只有大约 14 种被描述过。这些蛋白酶进一步分布在 26 个家族中,分为五个家族:天冬氨酸蛋白酶、半胱氨酸蛋白酶、金属蛋白酶、丝氨酸蛋白酶和苏氨酸蛋白酶。对金属蛋白酶类的关注进一步表明其在线粒体和质体加工中的作用,这表明金属蛋白酶作为可行的药物靶点具有潜力。全面了解寄生虫复杂的生命周期和鉴定潜在的药物靶点,对于开发有效的疟疾治疗策略和减轻其在全球的破坏性影响至关重要。

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