Ischemia-reperfusion (IR) injury is a damage to an organ when the blood supply is less than the demand required for normal functioning, leading to exacerbation of cellular dysfunction and death. IR injury occurs in different organs like the kidney, liver, heart, brain, etc., and may not only involve the ischemic organ but also cause systemic damage to distant organs. Oxygen-glucose deprivation in cells causes oxidative stress, calcium overloading, inflammation, and apoptosis. CREB is an essential integrator of the body’s various physiological systems, and it is widely accepted that dysfunction of CREB signaling is involved in many diseases, including ischemia-reperfusion injury. The activation of CREB can provide life to a cell and increase the cell’s survival after ischemia. Hence, GSK/CREB signaling pathway can provide significant protection to cells of different organs after ischemia and emerges as a futuristic strategy for managing ischemia-reperfusion injury. Different signaling pathways such as MAPK/ERK, TLR4/MyD88, RISK, Nrf2, and NF-κB, get altered during IR injury by the modulation of GSK-3 and CREB (cyclic AMP response element (CRE)–binding protein). GSK-3 (protein kinase B) and CREB are the downstream targets for fulfilling the roles of various signaling pathways. Calcium overloading during ischemia increases the expression of calcium-calmodulin-dependent protein kinase (CaMK), which subsequently activates CREB-mediated transcription, thus promoting the survival of cells. Furthermore, this review highlights the crosstalk between GSK-3 and CREB, promoting survival and rendering the cells resistant to subsequent severe ischemia.

缺血再灌注（IR）损伤是指当血液供应低于正常功能所需时对器官造成的损害，导致细胞功能障碍加剧和死亡。IR损伤发生在肾、肝、心、脑等不同器官，不仅可能累及缺血器官，还可能对远处器官造成全身性损伤。细胞中的氧葡萄糖缺乏会导致氧化应激、钙超载、炎症和细胞凋亡。CREB是人体各个生理系统的重要整合者，人们普遍认为CREB信号传导功能障碍与许多疾病有关，包括缺血再灌注损伤。CREB的激活可以为细胞提供生命并增加细胞在缺血后的存活率。因此，GSK/CREB信号通路可以为缺血后不同器官的细胞提供显着的保护，并成为治疗缺血再灌注损伤的未来策略。不同的信号通路，如 MAPK/ERK、TLR4/MyD88、RISK、Nrf2 和 NF-κB，在 IR 损伤期间通过 GSK-3 和 CREB（环 AMP 反应元件 (CRE) 结合蛋白）的调节而发生改变。GSK-3（蛋白激酶 B）和 CREB ​​是发挥各种信号通路作用的下游靶点。缺血期间钙超载会增加钙调蛋白依赖性蛋白激酶（CaMK）的表达，随后激活 CREB ​​介导的转录，从而促进细胞的存活。此外，这篇综述强调了 GSK-3 和 CREB ​​之间的串扰，促进细胞存活并使细胞对随后的严重缺血具有抵抗力。