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刚地弓形虫蛋白激酶:功能与药物靶点

Protein kinases of Toxoplasma gondii: functions and drug targets.

机构信息

College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, Changchun, 130118, People's Republic of China.

出版信息

Parasitol Res. 2013 Jun;112(6):2121-9. doi: 10.1007/s00436-013-3451-y. Epub 2013 May 17.

Abstract

Toxoplasma gondii is an important opportunistic parasite that infects almost all warm-blooded animals, causing congenital neurological and ocular diseases, especially in immunocompromised humans. The available therapeutic drugs are hypersensitive and toxic, and no vaccine is available to block the transmission of this parasite. Safer and more effective drugs are thus urgently needed to treat toxoplasmosis. Protein kinases (PKs) play crucial roles in the proliferation, differentiation, and pathogenesis of T. gondii. T. gondii calcium-dependent protein kinase 1 and cGMP-dependent protein kinase are associated with cell invasion; mitogen-activated protein kinase 1 and cAMP-dependent protein kinase are involved in stress response and conversion from tachyzoite to bradyzoite; casein kinase 1 and cdc2 cyclin-dependent kinase control cell cycle. Rhoptry kinases, the T. gondii-specific PKs, are involved in host manipulation. Because of their difference in structure and function from that of mammalian PKs, T. gondii PKs are promising drug targets. In this review, we describe the functions of T. gondii protein kinases and their inhibitors as potential drugs against T. gondii.

摘要

刚地弓形虫是一种重要的机会性寄生虫,几乎感染所有温血动物,导致先天性神经和眼部疾病,尤其是免疫功能低下的人类。现有的治疗药物高度敏感且有毒,没有疫苗可以阻断这种寄生虫的传播。因此,迫切需要更安全、更有效的药物来治疗弓形体病。蛋白激酶(PKs)在刚地弓形虫的增殖、分化和发病机制中发挥着关键作用。刚地弓形虫钙依赖性蛋白激酶 1 和 cGMP 依赖性蛋白激酶与细胞入侵有关;丝裂原活化蛋白激酶 1 和 cAMP 依赖性蛋白激酶参与应激反应和从速殖子向缓殖子的转化;酪蛋白激酶 1 和 cdc2 周期蛋白依赖性激酶控制细胞周期。裂殖体激酶是刚地弓形虫特有的 PKs,参与宿主操纵。由于其结构和功能与哺乳动物 PKs 的不同,刚地弓形虫 PKs 是有前途的药物靶点。在这篇综述中,我们描述了刚地弓形虫蛋白激酶的功能及其抑制剂作为抗刚地弓形虫的潜在药物。

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