Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway

Pharmacological activation of REV-ERBα reduces LPS-induced microglial activation in a dose-dependent manner.

• REV-ERBα is a transcriptional silencer that regulates genes related to inflammation and immune functions.
• Lipopolysaccharide (LPS) exposure triggers microglial activation, which is linked to neuroinflammation.
• Activation of REV-ERBα using agonists GSK4112 or SR9011 significantly suppresses the activation of microglia in vitro.
• The suppression of microglial activation is mediated through the nuclear factor kappa B (NF-κB) signaling pathway.
• Inhibition of NF-κB pathway components leads to reduced production of proinflammatory cytokines like IL-6 and TNFα.
• Enhanced activity of REV-ERBα protects neurons from damage caused by activated microglia.

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