The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model
Version 1

In the context of studying the role of the COP9 signalosome (CSN) in neuroinflammation and ischemic neuronal damage, we studied the effect of the cullin NEDDylation state-modifying drugs MLN4924 and CSN5i-3 in BV2 microglial cells, an immortalized murine cell line featuring many of the characteristics of primary microglia. Owing to its potent inhibitory effect on the NEDDylation cascade, MLN4924 exhibits a CSN5-like anti-inflammatory activity. Csn5i-3 is a small molecule inhibitor that specifically binds to CSN5, while it resides in the CSN holocomplex and blocks its deNEDDylase activity, thus leading to an accumulation of NEDDylated cullins. We performed untargeted mass spectrometry-based proteomics of the cell lysates after treating BV2 cells with these drugs under basal culture stress conditions. The proteomic analysis revealed that MLN4924 and CSN5i-3 substantially altered the microglial proteome.

SEEK ID: http://localhost:3000/data_files/70?version=1

help Creators and Submitter
Activity

Views: 122

Created: 9th Jul 2024 at 13:04

help Tags

This item has not yet been tagged.

help Attributions

None

Version History

Version 1 (earliest) Created 9th Jul 2024 at 13:04 by Rainer Malik

No revision comments

Powered by
(v.1.15.0)
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH