Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy.
Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy.
Cells. 2022 Dec 15;11(24):4061. doi: 10.3390/cells11244061.
Dimethyl fumarate (DMF) is a small molecule currently approved and used in the treatment of psoriasis and multiple sclerosis due to its immuno-modulatory, anti-inflammatory, and antioxidant properties. As an Nrf2 activator through Keap1 protein inhibition, DMF unveils a potential therapeutical use that is much broader than expected so far. In this comprehensive review we discuss the state-of-art and future perspectives regarding the potential repositioning of this molecule in the panorama of eye pathologies, including Age-related Macular Degeneration (AMD). The DMF's mechanism of action, an extensive analysis of the and evidence of its beneficial effects, together with a search of the current clinical trials, are here reported. Altogether, this evidence gives an overview of the new potential applications of this molecule in the context of ophthalmological diseases characterized by inflammation and oxidative stress, with a special focus on AMD, for which our gene-disease (-AMD) database search, followed by a protein-protein interaction analysis, further supports the rationale of DMF use. The necessity to find a topical route of DMF administration to the eye is also discussed. In conclusion, the challenge of DMF repurposing in eye pathologies is feasible and worth scientific attention and well-focused research efforts.
富马酸二甲酯(DMF)是一种小分子,由于其免疫调节、抗炎和抗氧化特性,目前已被批准用于治疗银屑病和多发性硬化症。作为一种通过抑制 Keap1 蛋白激活 Nrf2 的化合物,DMF 揭示了一种潜在的治疗用途,其范围比目前预期的要广泛得多。在这篇全面的综述中,我们讨论了该分子在眼部疾病(包括年龄相关性黄斑变性(AMD))领域重新定位的最新进展和未来前景。本文报道了 DMF 的作用机制、对其有益作用的广泛分析以及对当前临床试验的搜索。总之,这些证据概述了该分子在以炎症和氧化应激为特征的眼科疾病中的新的潜在应用,特别关注 AMD,我们对基因疾病(-AMD)数据库的搜索,随后进行蛋白质-蛋白质相互作用分析,进一步支持了 DMF 应用的合理性。还讨论了寻找 DMF 眼部局部给药途径的必要性。总之,DMF 在眼部疾病中的重新定位具有挑战性,但值得科学界关注和集中研究。