PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy
PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy
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DOI：
10.3892/ijmm.2014.1981
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发表时间：
2015-01-01
影响因子：
5.4
通讯作者：
Ogura, Yasunori
中科院分区：
文献类型：
--
作者：
Tokuhira, Nana;Kitagishi, Yasuko;Ogura, Yasunori
炎症性肠病（IBD），包括克罗恩病的发病机制，是一个越来越感兴趣的主题。含核苷酸结合寡聚化结构域蛋白2（NOD 2）的功能缺失突变是与克罗恩病相关的强遗传因素，其最终导致针对正常肠道微生物群组分的过度粘膜炎症反应。活性氧（ROS）在炎症过程中以及在从几种细胞因子（如肿瘤坏死因子（TNF））的受体的信号转导中起重要作用。活性氧通过PI 3 K/AKT/PTEN途径激活IB激酶（IKK）激活核因子-B（NF-B）。因此，该途径被认为在克罗恩病中起关键作用。功能丧失已被证明是多种疾病的早期事件。鉴于这种普遍参与许多疾病，调节这一途径的分子发展一直是几项研究的主题。此外，它一直是广泛研究和药物发现活动的焦点。更好地了解分子组装可能会揭示新的目标，治疗克罗恩病的发展。
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 (TNF). ROS activate nuclear factor-B (NF-B) via IB 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.