A multiplexed siRNA screen identifies key kinase signaling networks of brain glia.

Abstract

The dynamic behaviors of brain glial cells in various neuroinflammatory conditions and neurological disorders have been reported; however, little is known about the underlying intracellular signaling pathways. Here, we developed a multiplexed kinome-wide siRNA screen to identify the kinases regulating several inflammatory phenotypes of mouse glial cells in culture, including inflammatory activation, migration, and phagocytosis of glia. Subsequent proof-of-concept experiments involving genetic and pharmacological inhibitions indicated the importance of T-cell receptor signaling components in microglial activation and a metabolic shift from glycolysis to oxidative phosphorylation in astrocyte migration. This time- and cost-effective multiplexed kinome siRNA screen efficiently provides exploitable drug targets and novel insight into the mechanisms underlying the phenotypic regulation of glial cells and neuroinflammation. Moreover, the kinases identified in this screen may be relevant in other inflammatory diseases and cancer, wherein kinases play a critical role in disease signaling pathways.

• Authors: Jong-Heon Kim, Jin Han, Ruqayya Afridi, Jae-Hong Kim, Md Habibur Rahman, Dong Ho Park, Won Suk Lee, Gyun Jee Song, Kyoungho Suk
• Journal: Life science alliance (Life Sci Alliance) Vol. 6 Issue 5 (05 2023) ISSN: 2575-1077 [Electronic] United States
• PMID: 36878638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Kim et al.

Chemical References

• RNA, Small Interfering

Topics

• Animals
• Mice
• RNA, Small Interfering (genetics)
• Brain
• Neuroglia
• Signal Transduction
• Cell Movement