APOE and atherosclerosis: Moreover, applying MLN4924, a pharmacological inhibitor of the NEDD8-activating enzyme NAE1 thereby inhibiting the NEDDylation cascade, which mimics CSN5 hyperactivity and is used in clinical trials in patients with haematological and non-haematological malignancies [40–42], confirmed an anti-inflammatory activity of the CSN in macrophages, suggested a similar effect in inflammatory stimulated arterial endothelial cells, and led to partial atheroprotection in an Apoe–/– mouse-based in vivo model of atherosclerosis [43].