Activator or inhibitor? GSK-3 as a new drug target
Activator or inhibitor? GSK-3 as a new drug target
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DOI：
10.1016/j.bcp.2013.04.022
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发表时间：
2013-07-15
影响因子：
5.8
通讯作者：
Takahashi-Yanaga, Fumi
中科院分区：
文献类型：
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作者：
Takahashi-Yanaga, Fumi
糖原合酶激酶-3（GSK-3）是一种胞质丝氨酸/苏氨酸蛋白激酶，其磷酸化并抑制糖原合酶，从而抑制从葡萄糖合成糖原。然而，现在已知这种丝氨酸/苏氨酸激酶通过对细胞增殖、干细胞更新、凋亡和发育重要的许多信号传导途径来调节许多细胞过程。由于这些不同的作用，这种激酶的功能障碍也已知参与人类疾病的发病机制，例如神经系统疾病、糖尿病、骨形成、炎症、癌症和心力衰竭。因此，GSK-3被认为是开发新药的一个有吸引力的靶点。本文综述了GSK-3在胰岛素、Wnt/β-catenin和hedgehog信号通路中的作用及其活性调节。GSK-3在人类疾病发展中的作用，其参与各种信号通路的背景下也进行了总结。最后，针对这种激酶的新药开发的可能性进行了讨论与GSK-3的抑制剂和激活剂的最新信息。(C)2013 Elsevier Inc. All rights reserved.
Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase that phosphorylates and inhibits glycogen synthase, thereby inhibiting glycogen synthesis from glucose. However, this serine/threonine kinase is now known to regulate numerous cellular processes through a number of signaling pathways important for cell proliferation, stem cell renewal, apoptosis and development. Because of these diverse roles, malfunction of this kinase is also known to be involved in the pathogenesis of human diseases, such as nervous system disorders, diabetes, bone formation, Inflammation, cancer and heart failure. Therefore, GSK-3 is recognized as an attractive target for the development of new drugs. The present review summarizes the roles of GSK-3 in the insulin, Wnt/beta-catenin and hedgehog signaling pathways including the regulation of their activities. The roles of GSK-3 in the development of human diseases within the context of its participation in various signaling pathways are also summarized. Finally, the possibility of new drug development targeting this kinase is discussed with recent information about inhibitors and activators of GSK-3. (C) 2013 Elsevier Inc. All rights reserved.