SUMOylation and NEDDylation in kidney diseases

Kidney disease poses a serious threat to human health and life, while the lack of specific therapeutic targets hinders the treatment of kidney disease. Emerging evidence shows that post-translational modifications (PTMs), particularly SUMOylation and NEDDylation, two ubiquitin-like modifications, are potential therapeutic targets for kidney disease. SUMOylation and NEDDylation participate in the treatment of kidney diseases by regulating different substrate proteins and signaling pathways. In renal ischemia-reperfusion injury, the promotion of LKB1 SUMOylation and the inhibition of NEDDylation modification facilitate renal fibrosis, and the increase of HIF-1α deSUMOylation contributes to attenuating apoptosis and oxidative stress in the kidneys. In diabetic kidney disease (DKD), the suppression of IKKγ SUMOylation attenuates NF-κB inflammatory signaling, while the inhibition of STAT1 SUMOylation and RBMX SUMOylation alleviates renal fibrosis. Additionally, inhibiting Notch1 signaling SUMOylation reduces podocyte apoptosis and glomerular endothelial cell injury, while the suppression of RhoA NEDDylation decreases inflammation and fibrosis in DKD. Accumulated studies display the therapeutic effect of the activators and inhibitors of SUMOylation and NEDDylation against kidney diseases, such as TAK-981 and MLN4924. Therefore, SUMOylation and NEDDylation function as promising therapeutic targets for kidney diseases, and their activators and inhibitors may serve as novel candidates.