REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function

Inducible postnatal global deletion of both REV-ERB-α and -β leads to extensive transcriptional changes in the brain related to neurodegenerative pathways.

• Global deletion of REV-ERB-α and -β reveals significant changes in pathways associated with protein breakdown, immune response, and oxidative stress.
• Spontaneous activation of astrocytes occurs following the global deletion of both REV-ERB receptors.
• Astrocyte-specific deletion of REV-ERB-α and -β also results in increased astrocyte reactivity, indicating a cell-specific regulatory role.
• REV-ERB-α and -β are shown to repress certain genes related to astrocyte activation, with their deletion increasing STAT3 expression.
• Dual deletion of REV-ERBs enhances the uptake and degradation of alpha-synuclein in astrocytes and reduces associated pathology in a Parkinson's Disease model.

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