Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.
INSERM U1138, Centre des Cordeliers, 75270 Paris, France.
Cells. 2023 Feb 14;12(4):617. doi: 10.3390/cells12040617.
Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.
丝裂原活化蛋白激酶（MAPK）信号通路是普遍存在的细胞信号转导通路，调节生命的各个方面，并且在疾病中经常发生改变。这些 MAPK 一旦通过磷酸化激活，反过来又磷酸化并激活存在于细胞质或细胞核中的转录因子，导致靶基因的表达，从而引发各种生物学反应。这项工作的目的是提供一个全面的综述，重点介绍 MAPK 信号通路在眼生理病理学中的作用以及影响这些通路治疗眼部疾病的潜力。我们总结了目前在眼部疾病（如黄斑变性、白内障、青光眼和角膜病）以及细胞分化、增殖或迁移有缺陷的罕见眼部疾病中，针对 MAPK 的靶向化合物的相关知识。还讨论了潜在的治疗干预措施。此外，我们还讨论了克服一些 MAPK 抑制剂报道的眼部毒性的挑战。
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