Nuclear receptor 4A (NR4A) family - orphans no more.
Nuclear receptor 4A (NR4A) family - orphans no more.
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DOI：
10.1016/j.jsbmb.2015.04.016
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Tjalkens RB
中科院分区：
文献类型：
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作者：
Safe S;Jin UH;Morpurgo B;Abudayyeh A;Singh M;Tjalkens RB
孤儿核受体NR 4A 1、NR 4A 2和NR 4A 3是由多种应激刺激诱导的即刻早期基因，NR 4A 1受体在维持细胞稳态和疾病中起重要作用。越来越多的证据表明这些受体在代谢、心血管和神经功能中的作用，以及在炎症和炎性疾病中的作用，以及在免疫功能和癌症中的作用。尽管NR 4A 1、NR 4A 2和NR 4A 3的相似性以及它们与共同的顺式基因组元件的相互作用，但它们表现出独特的活性和细胞/组织特异性功能。尽管尚未鉴定出NR 4A受体的内源性配体，但越来越多的证据表明，结构多样的合成分子可以直接与NR 4A 1的配体结合结构域相互作用并充当激动剂或拮抗剂，并且还鉴定出NR 4A 2和NR 4A 3的配体。由于NR 4A受体是多种疾病的关键因素，因此NR 4A配体在未来的临床应用中有机会用于治疗多种健康问题，包括代谢、神经和心血管疾病、其他炎症和癌症。
The orphan nuclear receptors NR4A1, NR4A2 and NR4A3 are immediate early genes induced by multiple stressors, and the NR4A1 receptors play an important role in maintaining cellular homeostasis and disease. There is increasing evidence for the role of these receptors in metabolic, cardiovascular and neurological functions and also in inflammation and inflammatory diseases and in immune functions and cancer. Despite the similarities of NR4A1, NR4A2 and NR4A3 and their interactions with common cis-genomic elements, they exhibit unique activities and cell-/tissue-specific functions. Although endogenous ligands for NR4A receptors have not been identified, there is increasing evidence that structurally-diverse synthetic molecules can directly interact with the ligand binding domain of NR4A1 and act as agonists or antagonists, and ligands for NR4A2 and NR4A3 have also been identified. Since NR4A receptors are key factors in multiple diseases, there are opportunities for the future development of NR4A ligands for clinical applications in treating multiple health problems including metabolic, neurologic and cardiovascular diseases, other inflammatory conditions, and cancer.