Molecular Biology Interdepartmental PhD Program; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, United States.
Adv Parasitol. 2024;126:177-204. doi: 10.1016/bs.apar.2024.03.001. Epub 2024 Apr 14.
Parasitic nematodes infect over 2 billion individuals worldwide, primarily in low-resource areas, and are responsible for several chronic and potentially deadly diseases. Throughout their life cycle, these parasites are thought to use astacin metalloproteases, a subfamily of zinc-containing metalloendopeptidases, for processes such as skin penetration, molting, and tissue migration. Here, we review the known functions of astacins in human-infective, soil-transmitted parasitic nematodes - including the hookworms Necator americanus and Ancylostoma duodenale, the threadworm Strongyloides stercoralis, the giant roundworm Ascaris lumbricoides, and the whipworm Trichuris trichiura - as well as the human-infective, vector-borne filarial nematodes Wuchereria bancrofti, Onchocerca volvulus, and Brugia malayi. We also review astacin function in parasitic nematodes that infect other mammalian hosts and discuss the potential of astacins as anthelmintic drug targets. Finally, we highlight the molecular and genetic tools that are now available for further exploration of astacin function and discuss how a better understanding of astacin function in human-parasitic nematodes could lead to new avenues for nematode control and drug therapies.
寄生虫线虫感染全球超过 20 亿人，主要集中在资源匮乏的地区，并且可导致多种慢性和潜在致命疾病。在整个生命周期中，这些寄生虫被认为利用天冬氨酸蛋白酶，即含锌金属内肽酶的一个亚家族，来完成皮肤穿透、蜕皮和组织迁移等过程。在此，我们综述了天冬氨酸蛋白酶在人源感染性、土壤传播性寄生虫线虫中的已知功能，包括美洲钩虫、十二指肠钩虫、粪类圆线虫、蛔虫和鞭虫，以及人源感染性、媒介传播性丝虫班氏吴策线虫、盘尾丝虫和马来丝虫。我们还综述了感染其他哺乳动物宿主的寄生虫线虫中天冬氨酸蛋白酶的功能，并讨论了天冬氨酸蛋白酶作为驱虫药物靶点的潜力。最后，我们重点介绍了目前可用于进一步研究天冬氨酸蛋白酶功能的分子和遗传工具，并讨论了对人源寄生虫线虫中天冬氨酸蛋白酶功能的更好理解如何为线虫控制和药物治疗开辟新途径。
