Sun Yuxin, Hao Mengyu, Wu Hao, Zhang Chengzhi, Wei Dong, Li Siyu, Song Zongming, Tao Ye
Department of Ophthalmology, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
College of Medicine, Zhengzhou University, Zhengzhou, 450001, China.
Cell Biosci. 2024 May 9;14(1):59. doi: 10.1186/s13578-024-01236-2.
Ca/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca-dependent signaling pathways. Its significance as an intracellular Ca sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.
钙/钙调蛋白依赖性蛋白激酶II（CaMKII）是一类底物特异性广泛的丝氨酸（Ser）/苏氨酸（Thr）蛋白激酶，在钙依赖性信号通路中起关键作用。其作为细胞内钙传感器的重要性在神经退行性变领域引发了大量研究兴趣。越来越多的证据表明，CaMKII与糖尿病性视网膜病变（DR）、年龄相关性黄斑变性（AMD）、视网膜色素变性（RP）和青光眼性视神经病变等退行性视网膜病变的病理过程有关。CaMKII可诱导视网膜血管异常增殖，影响突触信号传导，并对视网膜神经节细胞和色素上皮细胞的存活产生双重影响。研究人员已经提出了多种治疗药物，包括具有调节CaMKII活性能力的小分子、肽和核苷酸。由于其广泛的同工型和剪接变体，旨在特异性抑制CaMKII的治疗策略面临着相当大的挑战。因此，识别CaMKII的有害和有益方面变得至关重要，从而促进有效治疗方法的开发。在这篇综述中，我们总结了关于CaMKII细胞和分子生物学的最新研究结果，特别强调其代谢和调节机制。我们深入探讨了CaMKII在视网膜信号转导通路中的作用，并讨论了CaMKII与钙超载之间的关系。此外，我们阐述了针对CaMKII的治疗试验，并介绍了CaMKII抑制剂领域的最新进展。这些发现将丰富我们对CaMKII的认识，并为退行性视网膜病变治疗靶点的开发提供启示。
