Effects of the Nrf2 signaling pathway on the occurrence and development of cataract / 中华实验眼科杂志

ABSTRACT

Cataract is the leading cause of blindness worldwide, and the common mechanism for its onset and development is oxidative damage to the lens.The expression of a large number of antioxidant genes is regulated by nuclear factor erythroid 2-related factor 2 (Nrf2), and the Nrf2 oxidative defense system is one of the main defense systems for antioxidant damage in the body.The activity of Nrf2 signaling pathway is primarily regulated by Kelch-like ECH-associated protein 1 (Keap1), and Keap1 mediates Nrf2 protein degradation thereby inhibiting the activation of the Nrf2 pathway in a Keap1-dependent manner.Increasing research has revealed other mechanisms of Nrf2 regulation in a Keap1-independent manner, including phosphorylation and acetylation of Nrf2 (PKC, PI3K/Akt, JNK, and P300/CBP) and epigenetic factors (promoter methylation, histone modification, and microRNAs-144, -28 and -34). Reduced expression of Nrf2 and its downstream antioxidant genes has been shown to play an important role in the onset and development of various types of cataracts.Many compounds, such as morin, hyperoside, sulforaphane, rosae laevigatae extract, 3-n-butylphthalide, and acetyl-L-carnitine, have been found to be able to upregulate the expression of antioxidant genes by activating Nrf2 signaling pathway to protect lens epithelial cells from oxidative stress to prevent or alleviate cataract.This article reviewed recent researches on Nrf2 signaling pathway and the relationship between Nrf2 activators and cataract to provide a theoretical basis for the prevention and treatment of cataract.