Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

• DOI: 10.1126/sciadv.abc5539
• Publication Date: 2021-01-20T20:15:19Z
• Authors: Xing Li; Qian Xia; Meng Mao; Huijuan Zhou; Lu Zheng; Yi Wang; Zhen Zeng; Lulu Yan; Yin Zhao; Jing Shi
• Keywords: Annexin A1; IκB kinase; S-Nitrosoglutathione

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated could promote beneficial phenotype polarization of microglia. Mechanistically, suppressed nuclear factor κB production proinflammatory mediators. Further study revealed targeted IκB kinase (IKK) complex selectively enhanced IKKα degradation. Simultaneously, detected facilitated interaction between NBR1 degradation through selective autophagy. work overexpression microglia/macrophages resulted marked improvement neurological function mouse model cerebral ischemia. Collectively, our demonstrates previously unidentified whereby regulates strongly indicates up-regulation SUMOylation microglia may provide therapeutic benefits for