1. REV-ERBα Mitigates Astrocyte Activation and Protects Dopaminergic Neurons from Damage.
- Author
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Wang X, Zhi H, Zhang Z, Li J, and Guo D
- Subjects
- Animals, Mice, Cells, Cultured, NF-kappa B metabolism, STAT3 Transcription Factor metabolism, STAT3 Transcription Factor genetics, Apoptosis, Mice, Inbred C57BL, Signal Transduction, Astrocytes metabolism, Astrocytes drug effects, Nuclear Receptor Subfamily 1, Group D, Member 1 metabolism, Nuclear Receptor Subfamily 1, Group D, Member 1 genetics, Dopaminergic Neurons metabolism
- Abstract
Parkinson's disease (PD) is characterized by astrocyte activation and disruptions in circadian rhythm. Within the astrocyte population, two distinct reactive states exist: A1 and A2. A1 astrocytes are associated with neurotoxicity and inflammation, while A2 astrocytes exhibit neuroprotective functions. Our investigation focused on the role of REV-ERBα, a member of the nuclear receptor superfamily and a key regulator of the circadian clock, in astrocyte activation. We observed that REV-ERBα expression in A1 astrocytes was reduced to one-third of its normal level. Notably, activation of REV-ERBα prompted a transformation of astrocytes from A1 to A2. Mechanistically, REV-ERBα inhibition was linked to the classical NF-κB pathway, while it concurrently suppressed the STAT3 pathway. Furthermore, astrocytes with low REV-ERBα expression were associated with dopaminergic neurons apoptosis. Intriguingly, the opposite effect was observed when using a REV-ERBα agonist, which mitigated astrocyte activation and reduced dopaminergic neuron damage by 50%. In summary, our study elucidates the pivotal role of REV-ERBα in modulating astrocyte function and its potential implications in PD pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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