PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review)

Tokuhira,Nana; Kitagishi,Yasuko; Suzuki,Miho; Minami,Akari; Nakanishi,Atsuko; Ono,Yuna; Kobayashi,Keiko; Matsuda,Satoru; Ogura,Yasunori

doi:10.3892/ijmm.2014.1981

PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review)

Authors:
- Nana Tokuhira
- Yasuko Kitagishi
- Miho Suzuki
- Akari Minami
- Atsuko Nakanishi
- Yuna Ono
- Keiko Kobayashi
- Satoru Matsuda
- Yasunori Ogura
View Affiliations

Affiliations: Department of Food Science and Nutrition, Nara Women's University, Nara 630‑8506, Japan
Published online on: October 27, 2014 https://doi.org/10.3892/ijmm.2014.1981
Pages: 10-16

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Abstract

The pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease, is a subject of increasing interest. Loss-of-function mutations in nucleotide‑binding oligomerization domain-containing protein 2 (NOD2) are strong genetic factors linked to Crohn's disease, which eventually leads to an excessive mucosal inflammatory response directed against components of normal gut microbiota. Reactive oxygen species (ROS) play an important role in inflammation processes, as well as in transduction of signals from receptors for several cytokines, such as tumor necrosis factor α (TNFα). ROS activate nuclear factor‑κB (NF‑κB) via IκB kinase (IKK) through the PI3K/AKT/PTEN pathway. Therefore, this pathway is recognized to play a key role in Crohn's disease. Loss of function has been demonstrated to occur as an early event in a wide variety of diseases. Given this prevalent involvement in a number of diseases, the molecular development that modulates this pathway has been the subject of several studies. In addition, it has been the focus of extensive research and drug discovery activities. A better understanding of the molecular assemblies may reveal novel targets for the therapeutic development against Crohn's disease.

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