环磷酸腺苷反应元件结合蛋白CREB相关信号通路研究进展
Research Progress of Signal Pathways Related to Cyclic Adenosine Phosphate Reaction Element Binding Protein CREB
DOI: 10.12677/acm.2025.151104, PDF,  被引量    科研立项经费支持
作者: 胡可鑫*, 李珮荣*, 杨泽睿, 杨雨佳, 张顺禹：内蒙古医科大学第一临床医学院，内蒙古 呼和浩特；杨光路#：内蒙古医科大学附属医院儿科，内蒙古 呼和浩特
关键词: CREB；信号通路；神经系统；肿瘤；疼痛；CREB； Signaling Pathways； Nervous System； Tumors； Pain
摘要: 本研究旨在剖析环磷酸腺苷反应元件结合蛋白(CAMP Response Element Binding protein, CREB)相关的三种信号通路在疾病中的作用机制，以期为疾病治疗提供创新性的策略。我们采用综述的形式，通过计算机检索PubMed数据库、中国知网等权威资源，筛选并整理与CREB信号通路相关的文献资料，进行了系统的分析和探讨。在ERK/CREB信号通路的研究中，我们发现该通路对长期记忆的形成具有破坏作用以及加速抑郁症的发展。在cAMP-PKA-CREB信号通路的研究中，我们发现这一通路对乳腺癌、肺癌等多种肿瘤疾病的进展具有重要影响。同时，在CaMKII/CREB/BDNF信号通路的研究中，我们发现该通路在疼痛的维持和产生过程中起到关键作用。综上所述，我们认为CREB及其信号通路在神经系统疾病、肿瘤疾病等多种疾病中发挥着至关重要的作用。
Abstract: The aim of this study is to analyze the mechanism of action of three signaling pathways related to CAMP Response Element Binding protein (CREB) in diseases, with a view to providing innovative strategies for disease treatment. In the form of a review, we searched authoritative resources such as PubMed database and CNKI by computer, screened and sorted out literature related to CREB signaling pathway, and carried out a systematic analysis and discussion. In our study of the ERK/CREB signaling pathway, we found that this pathway has a destructive effect on long-term memory formation and accelerates the development of depression. In the study of cAMP-PKA-CREB signaling pathway, we found that this pathway has an important impact on the progression of breast cancer, lung cancer and other tumor diseases. At the same time, in the study of CaMKII/CREB/BDNF signaling pathway, we found that this pathway plays a key role in the maintenance and production of pain. In summary, we believe that CREB and its signaling pathway play a crucial role in a variety of diseases, such as neurological diseases and tumor diseases.
文章引用：胡可鑫, 李珮荣, 杨泽睿, 杨雨佳, 张顺禹, 杨光路. 环磷酸腺苷反应元件结合蛋白CREB相关信号通路研究进展[J]. 临床医学进展, 2025, 15(1): 771-776. https://doi.org/10.12677/acm.2025.151104

参考文献

[1] Ichiki, T. (2006) Role of cAMP Response Element Binding Protein in Cardiovascular Remodeling: Good, Bad, or Both? Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 449-455. [Google Scholar] [CrossRef] [PubMed]
[2] Xu, W., Kasper, L.H., Lerach, S., Jeevan, T. and Brindle, P.K. (2007) Individual CREB-Target Genes Dictate Usage of Distinct cAMP-Responsive Coactivation Mechanisms. The EMBO Journal, 26, 2890-2903. [Google Scholar] [CrossRef] [PubMed]
[3] Sun, L., Zhao, R., Zhang, L., Zhang, W., He, G., Yang, S., et al. (2016) Prevention of Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by CREB-Mediated P21 Induction: An Insight from a Plant Polyphenol. Biochemical Pharmacology, 103, 40-52. [Google Scholar] [CrossRef] [PubMed]
[4] Naqvi, S., Martin, K.J. and Arthur, J.S.C. (2014) CREB Phosphorylation at Ser133 Regulates Transcription via Distinct Mechanisms Downstream of cAMP and MAPK Signalling. Biochemical Journal, 458, 469-479. [Google Scholar] [CrossRef] [PubMed]
[5] Johannessen, M., Delghandi, M.P. and Moens, U. (2004) What Turns CREB on? Cellular Signalling, 16, 1211-1227. [Google Scholar] [CrossRef] [PubMed]
[6] Steven, A., Friedrich, M., Jank, P., Heimer, N., Budczies, J., Denkert, C., et al. (2020) What Turns CREB on? and off? and Why Does It Matter? Cellular and Molecular Life Sciences, 77, 4049-4067. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, Y., Zhu, Z., Liang, H., Zhang, L., Zhou, Q., Ni, H., et al. (2018) nNOS-CAPON Interaction Mediates Amyloid‐β‐Induced Neurotoxicity, Especially in the Early Stages. Aging Cell, 17, e12754. [Google Scholar] [CrossRef] [PubMed]
[8] Chong, C., Ke, M., Tan, Y., Huang, Z., Zhang, K., Ai, N., et al. (2018) Presenilin 1 Deficiency Suppresses Autophagy in Human Neural Stem Cells through Reducing Γ-Secretase-Independent ERK/CREB Signaling. Cell Death & Disease, 9, Article No. 879. [Google Scholar] [CrossRef] [PubMed]
[9] Zhang, L., Xie, J., Yang, J. and Cao, Y. (2013) Tyrosine Phosphatase STEP61 Negatively Regulates Amyloid β‐Mediated ERK/CREB Signaling Pathways via α7 Nicotinic Acetylcholine Receptors. Journal of Neuroscience Research, 91, 1581-1590. [Google Scholar] [CrossRef] [PubMed]
[10] Liu, X., Hou, Z., Han, M., Chen, K., Wang, Y., Qing, J., et al. (2022) Salvianolic Acid B Alleviates Comorbid Pain in Depression Induced by Chronic Restraint Stress through Inhibiting GABAergic Neuron Excitation via an ERK-CREB-BDNF Axis-Dependent Mechanism. Journal of Psychiatric Research, 151, 205-216. [Google Scholar] [CrossRef] [PubMed]
[11] Guan, L., Jia, N., Zhao, X., Zhang, X., Tang, G., Yang, L., et al. (2013) The Involvement of ERK/CREB/Bcl-2 in Depression-Like Behavior in Prenatally Stressed Offspring Rats. Brain Research Bulletin, 99, 1-8. [Google Scholar] [CrossRef] [PubMed]
[12] Peng, H., Wang, H.B., Wang, L., Zhou, B., Li, X.Y. and Tan, J. (2018) Gsk3β Aggravates the Depression Symptoms in Chronic Stress Mouse Model. Journal of Integrative Neuroscience, 17, 169-175. [Google Scholar] [CrossRef] 
[13] Sola-Penna, M., Paixão, L.P., Branco, J.R., Ochioni, A.C., Albanese, J.M., Mundim, D.M., et al. (2019) Serotonin Activates Glycolysis and Mitochondria Biogenesis in Human Breast Cancer Cells through Activation of the Jak1/STAT3/ERK1/2 and Adenylate Cyclase/PKA, Respectively. British Journal of Cancer, 122, 194-208. [Google Scholar] [CrossRef] [PubMed]
[14] Yu, T., Yang, G., Hou, Y., Tang, X., Wu, C., Wu, X., et al. (2016) Cytoplasmic GPER Translocation in Cancer-Associated Fibroblasts Mediates cAMP/PKA/CREB/Glycolytic Axis to Confer Tumor Cells with Multidrug Resistance. Oncogene, 36, 2131-2145. [Google Scholar] [CrossRef] [PubMed]
[15] Cho, E., Kim, E., Kwak, S. and Juhnn, Y. (2014) cAMP Signaling Inhibits Radiation-Induced ATM Phosphorylation Leading to the Augmentation of Apoptosis in Human Lung Cancer Cells. Molecular Cancer, 13, Article No. 36. [Google Scholar] [CrossRef] [PubMed]
[16] Choi, Y.J., Kim, S., Oh, J. and Juhnn, Y. (2009) Stimulatory Heterotrimeric G Protein Augments Gamma Ray-Induced Apoptosis by Up-Regulation of Bak Expression via CREB and AP-1 in H1299 Human Lung Cancer Cells. Experimental and Molecular Medicine, 41, 592-600. [Google Scholar] [CrossRef] [PubMed]
[17] Su, H., Chen, H., Zhang, X., Su, S., Li, J., Guo, Y., et al. (2023) Electroacupuncture Ameliorates Pain in Cervical Spondylotic Radiculopathy Rat by Inhibiting the CaMKII/CREB/BDNF Signaling Pathway and Regulating Spinal Synaptic Plasticity. Brain and Behavior, 13, e3177. [Google Scholar] [CrossRef] [PubMed]
[18] Fang, L., Wu, J., Lin, Q. and Willis, W.D. (2002) Calcium-Calmodulin-Dependent Protein Kinase II Contributes to Spinal Cord Central Sensitization. The Journal of Neuroscience, 22, 4196-4204. [Google Scholar] [CrossRef] [PubMed]
[19] He, R., Fan, J., Qian, F., He, Y., Du, X. and Lu, H. (2023) Repetitive Transcranial Magnetic Stimulation Promotes Neurological Functional Recovery in Rats with Traumatic Brain Injury by Upregulating Synaptic Plasticity-Related Proteins. Neural Regeneration Research, 18, 368-374. [Google Scholar] [CrossRef] [PubMed]
[20] Zhang, X., Lun, M., Du, W., Ma, F. and Huang, Z. (2022) The κ-Opioid Receptor Agonist U50488H Ameliorates Neuropathic Pain through the Ca2+/CaMKII/CREB Pathway in Rats. Journal of Inflammation Research, 15, 3039-3051. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, Y., Cheng, X., Xu, J., Liu, Z., Wan, Y. and Ma, D. (2010) Anti-Hyperalgesic Effect of CaMKII Inhibitor Is Associated with Downregulation of Phosphorylated CREB in Rat Spinal Cord. Journal of Anesthesia, 25, 87-92. [Google Scholar] [CrossRef] [PubMed]
[22] Luo, Y., Kuang, S., Li, H., Ran, D. and Yang, J. (2017) cAMP/PKA-CREB-BDNF Signaling Pathway in Hippocampus Mediates Cyclooxygenase 2-Induced Learning/Memory Deficits of Rats Subjected to Chronic Unpredictable Mild Stress. Oncotarget, 8, 35558-35572. [Google Scholar] [CrossRef] [PubMed]
[23] Chen, D.Y., Bambah-Mukku, D., Pollonini, G. and Alberini, C.M. (2012) Glucocorticoid Receptors Recruit the CaMKII α-BDNF-CREB Pathways to Mediate Memory Consolidation. Nature Neuroscience, 15, 1707-1714. [Google Scholar] [CrossRef] [PubMed]

为你推荐