PI3K/AKT signaling in parasites and parasite diseases: Role and therapeutic potential
Lujun Yan, Yating Li, Xing Yang, Rui Li, Chunyin Zhu, Xuedong He, Xiaoliang Jin, Guanghui Zheng, Naunain Mehmood, William C. Cho, Shijun Bao, Houhui Song, Yadong Zheng
Abstract
Parasite diseases pose a significant threat due to the serious harm they cause to hosts, and developing affordable drugs for treatment presents enormous challenges. "Target repurposing" has emerged as a promising strategy to overcome this difficulty by leveraging the drug targets for human diseases and matching them with homologs in parasites. The PI3K/AKT signaling pathway, known for its crucial role in regulating malignant cell proliferation, migration, and invasion, has been validated as a drug target for cancer. Interestingly, the PI3K/AKT signaling pathway is also involved in parasite development, infection, and survival within the hosts. During infection, parasites can exploit the host's PI3K/AKT signaling, which influences immune cell apoptosis, macrophage activation, regulatory T cell functions, and the communication between immune cells, thus facilitating chronic infection. The immunoregulatory functions of the PI3K/AKT signaling make its inhibitors promising candidates for the control of parasite diseases. This review mainly outlines the characteristics and functions of the PI3K/AKT signaling pathway during parasite infection and further provides an overview of the drugs targeting the PI3K/AKT signaling pathway for treating parasite diseases.