PDF(Pubmed)
Abstract：
Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, β, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism in E. granulosus s.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of E. granulosus sensu stricto (s.s.) and disrupted the ultrastructure. The results of in vivo experiments showed that the AMPK inhibitor had a significant therapeutic effect on E. granulosus s.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions in E. granulosus s.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.
摘要：
囊性棘球蚴病（CE）是由细粒棘球蚴（s.l.）群的幼虫引起的人畜共患寄生虫病。迫切需要开发新的药物靶标和药物分子来治疗CE。腺苷一磷酸（AMP）激活的蛋白激酶（AMPK），丝氨酸/苏氨酸蛋白激酶由α，β,和γ亚基，在能量代谢的调节中起着关键作用。然而,AMPK在S.I.中调节葡萄糖代谢的作用及其对寄生虫活力的影响尚不清楚。在这项研究中,我们发现EgAMPKα或小分子AMPK抑制剂的靶向敲除抑制了S.S.的活力，并破坏了超微结构。体内实验结果表明,AMPK抑制剂对细粒E.S.感染小鼠有明显的治疗作用,并导致生发层细胞结构的丧失。此外,EgAMPK/EgGLUT1途径的抑制限制了细粒大肠杆菌的葡萄糖摄取和葡萄糖代谢功能。总的来说,我们的研究结果表明,EgAMPK可能是CE的潜在药物靶点,抑制EgAMPK活化是治疗疾病的有效策略.
