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Updated: May 26, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Serum amyloid A drive microglia shift to a resolving phenotype through Nrf2
Qi Li1, Yiwei Huang1, Tao Ban1
1Jiangsu Key Laboratory of Neuropsychiatric Diseases and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China.
Abstract:
Serum amyloid A (SAA) is an acute-phase protein that has been recognized as a diagnostic biomarker for several diseases. However, the functional studies about the effects of SAA on microglial activation seem controversial. Here, we discovered that SAA induces microglial cells polarize to a pro-resolving M2 phenotype by promoting the stability of the transcription factor Nrf2, which specifically regulates microglia towards a pro-resolving phenotype via metabolic reprogramming. Moreover, we identified that the AMPK/mTOR signaling pathway is involved in SAA-induced Nrf2 upregulation. Additionally, SAA protects cultured neuronal cells from MPP+-induced damage, and furthermore, local administration of SAA into the substantia nigra significantly attenuated MPTP-induced dopaminergic neuronal loss, thereby improving motor impairments in mice. In conclusion, for the first time we demonstrate SAA regulate microglial activation by promoting Nrf2 stabilization, ultimately protecting dopaminergic neurons and alleviating MPTP-induced PD-like pathology.
Insights
Serum amyloid A (SAA) promotes a pro-resolving microglial phenotype by stabilizing Nrf2, protecting dopaminergic neurons and alleviating Parkinson
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Serum amyloid A (SAA) is an acute-phase protein with diagnostic potential.
- The role of SAA in microglial activation is debated.
- Microglial activation is critical in neuroinflammation and neurodegenerative diseases.
Purpose of the Study:
- To elucidate the functional role of SAA in microglial activation.
- To investigate SAA's effects on neuroprotection in Parkinson's disease models.
Main Methods:
- Investigated SAA's effect on microglial polarization.
- Analyzed the role of Nuclear factor erythroid 2-related factor 2 (Nrf2) and the AMPK/mTOR pathway.
- Utilized in vitro neuronal cultures and an in vivo mouse model of Parkinson's disease (MPTP-induced).
Main Results:
- SAA induces pro-resolving M2 microglial polarization via Nrf2 stabilization.
- The AMPK/mTOR pathway mediates SAA-induced Nrf2 upregulation.
- SAA protects neurons from MPP+-induced damage and attenuates MPTP-induced dopaminergic neurodegeneration in mice, improving motor function.
Conclusions:
- SAA regulates microglial activation through Nrf2 stabilization, promoting a pro-resolving phenotype.
- SAA demonstrates neuroprotective effects against Parkinson's disease pathology.
- SAA represents a potential therapeutic target for Parkinson's disease.
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