ArticleInflammation2025
Inhibition of Cullin3 Neddylation Alleviates Diabetic Retinopathy by Activating Nrf2 Signaling to Combat ROS-Induced Oxidative Stress and Inflammation.
Article in Inflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Identification and analysis of oxidative stress-related genes associated with the occurrence and development of diabetic retinopathy.Scientific reports · 2026Article
- From risk factors to molecular targets: clinical associations and molecular docking insights into phthalate-associated diabetic retinopathy.Frontiers in medicine · 2026Article
- N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.Redox biology · 2025Article
- Article
- A new perspective on protecting the blood-retinal barrier against injury in diabetic retinopathy: mitophagy.Frontiers in endocrinology · 2025Review
- Research progress on Nrf2 intervention in the treatment of diabetic retinopathy.Frontiers in endocrinology · 2025Review
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Authors and funding
10 authors.
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Abstract
Oxidative stress and inflammation induced by reactive oxygen species (ROS) play important roles in the development of diabetic retinopathy (DR). Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which is negatively controlled by Cullin3-RING E3 ligase (CRL3) and controls ROS levels, is compromised in DR. CRL3 activity is regulated by Cullin3 neddylation. Nonetheless, the relationship between Cullin3 neddylation and DR remains uncertain. The goal of this study was to evaluate the effect of Cullin3 neddylation on DR and its underlying mechanisms by utilizing MLN4924, a neddylation inhibitor. Cullin3 neddylation was elevated in diabetic rats' retinas as well as in advanced glycation end products (AGEs)-induced endothelial cells. Inhibiting neddylation of Cullin3 with MLN4924 downregulated Nrf2 ubiquitination, promoted Nrf2 accumulation, suppressed ROS-induced oxidative stress and inflammation, and attenuated blood-retinal barrier (BRB) breakdown in both diabetic vivo and vitro models. However, the beneficial impact of MLN4924 was compromised when Nrf2 was suppressed with siRNA in vitro. This study showed that inhibition of Cullin3 neddylation with MLN4924 exerted protective effect on DR by activating Nrf2 signaling to inhibit ROS-induced retinal injury, which indicated that targeting Cullin3 neddylation could be a promising treatment option for DR.
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