A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation
- A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation
- 이상희; 남영표; 구자영; 임동현; 박종민; 옥지연; 김재홍; 석경호; 박승범
- Issue Date
- Nature chemical biology
- VOL 10, NO 12-1060
- Because of the critical role of neuroinflammation in various neurological diseases, there are continuous efforts to identify new therapeutic targets as well as new therapeutic agents to treat neuroinflammatory diseases. Here we report the discovery of inflachromene (ICM), a microglial inhibitor with anti-inflammatory effects. Using the convergent strategy of phenotypic screening with early stage target identification, we show that the direct binding target of ICM is the high mobility group box (HMGB) proteins. Mode-of-action studies demonstrate that ICM blocks the sequential processes of cytoplasmic localization and extracellular release of HMGBs by perturbing its post-translational modification. In addition, ICM effectively downregulates proinflammatory functions of HMGB and reduces neuronal damage in vivo. Our study reveals that ICM suppresses microglia-mediated inflammation and exerts a neuroprotective effect, demonstrating the therapeutic potential of ICM in neuroinflammatory diseases.
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