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

• Published in: International journal of molecular medicine Vol. 35; no. 1; pp. 10 - 16
• Main Authors: TOKUHIRA, NANA, KITAGISHI, YASUKO, SUZUKI, MIHO, MINAMI, AKARI, NAKANISHI, ATSUKO, ONO, YUNA, KOBAYASHI, KEIKO, MATSUDA, SATORU, OGURA, YASUNORI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.01.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: AKT; Animals; Apoptosis; Crohn Disease - drug therapy; Crohn Disease - metabolism; Crohn's disease; Cytokines; Diet; Disease; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Genetic aspects; Humans; Inflammation; Inflammatory bowel disease; Inflammatory diseases; Kinases; mammalian target of rapamycin; Molecular Targeted Therapy; Nod2 Signaling Adaptor Protein - metabolism; nucleotide-binding oligomerization domain-containing protein 2; Pathogens; Phosphatase; phosphatase and tensin homolog; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Physiological aspects; Protein kinases; Proteins; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; Quality of life; Reactive oxygen species; Regulation; Risk factors; Signal transduction; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Tumor necrosis factor-TNF; Japan
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2014.1981

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.