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REV-ERBα Mitigates Astrocyte Activation and Protects Dopaminergic Neurons from Damage.
- Source :
- Journal of Molecular Neuroscience; Sep2024, Vol. 74 Issue 3, p1-11, 11p
- Publication Year :
- 2024
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08958696
- Volume :
- 74
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Molecular Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 179627158
- Full Text :
- https://doi.org/10.1007/s12031-024-02264-w