A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation

Title
A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation
Authors
이상희남영표구자영임동현박종민옥지연김재홍석경호박승범
Issue Date
2014-12
Publisher
Nature chemical biology
Citation
VOL 10, NO 12-1060
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/67445
ISSN
1552-4469
Appears in Collections:
KIST Publication > Article
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