Lanthionine Synthetase Component C-Like Protein 2: A New Drug Target for Inflammatory Diseases and Diabetes
Lanthionine Synthetase Component C-Like Protein 2: A New Drug Target for Inflammatory Diseases and Diabetes
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DOI：
10.2174/1389450115666140313123714
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Bassaganya-Riera, Josep
中科院分区：
文献类型：
--
作者：
Lu, Pinyi;Hontecillas, Raquel;Bassaganya-Riera, Josep
羊毛硫氨酸合成酶成分 C 样蛋白 2 (LANCL2) 是 LANCL 蛋白家族的成员，在全身广泛表达。 LANCL2 是脱落酸 (ABA) 的分子靶标，脱落酸是一种具有胰岛素增敏和免疫调节作用的化合物。 LANCL2 是免疫细胞中 ABA 膜结合和信号传导所必需的。使用分子建模方法在计算机上预测了 ABA 与 LANCL2 的直接结合，并使用配体结合测定和动力学表面等离子共振研究进行了实验验证。 LANCL2 通路的治疗潜力包括提高细胞对抗癌药物的敏感性、胰岛素增敏作用以及在免疫介导疾病和传染病中调节免疫和炎症反应。 NSC61610等新型LANCL2配体对小鼠炎症性肠病和流感引起的炎症的抗炎活性也说明了基于LANCL2的药物发现和开发的案例。本综述讨论了 LANCL2 作为发现和开发针对慢性代谢性疾病、免疫介导疾病和传染病的新型口服活性药物的新治疗靶点的价值。
Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the LANCL protein family, which is broadly expressed throughout the body. LANCL2 is the molecular target of abscisic acid (ABA), a compound with insulin-sensitizing and immune modulatory actions. LANCL2 is required for membrane binding and signaling of ABA in immune cells. Direct binding of ABA to LANCL2 was predicted in silico using molecular modeling approaches and validated experimentally using ligand-binding assays and kinetic surface plasmon resonance studies. The therapeutic potential of the LANCL2 pathway ranges from increasing cellular sensitivity to anticancer drugs, insulin-sensitizing effects and modulating immune and inflammatory responses in the context of immune-mediated and infectious diseases. A case for LANCL2-based drug discovery and development is also illustrated by the anti-inflammatory activity of novel LANCL2 ligands such as NSC61610 against inflammatory bowel disease and influenza-driven inflammation in mice. This review discusses the value of LANCL2 as a novel therapeutic target for the discovery and development of new classes of orally active drugs against chronic metabolic, immune-mediated and infectious diseases.