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Published on: August 23, 2024
MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κB and PI3K-Akt pathways
Xiaotian Xu1, Aiwu Zhang1, Yingting Zhu2
1Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Abstract:
Recent evidence have suggested that neuroinflammation and ischemia induce the activation of two different types of reactive astrocytes, termed A1 and A2. Additionally, A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative diseases, such as Alzheimer's disease (AD). In the current study, we constructed an Aβ42-activated microglia-conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG-E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor-κB and the upregulation of PI3K-Akt. This study showed that MFG-E8 suppressed A1 astrocytes and holds great potential for the treatment of AD.
Insights
Milk fat globule epidermal growth factor 8 (MFG-E8) suppresses harmful A1 astrocytes, offering potential treatment for Alzheimer's disease (AD) by modulating neuroinflammation and neuronal death.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation and ischemia activate reactive astrocytes (A1 and A2 types).
- A1 astrocytes contribute to neuronal and oligodendrocyte death in neurodegenerative diseases like Alzheimer's disease (AD).
Purpose of the Study:
- To investigate the role of milk fat globule epidermal growth factor 8 (MFG-E8) in regulating A1/A2 astrocytic activation.
- To explore MFG-E8's potential therapeutic effects in Alzheimer's disease models.
Main Methods:
- Constructed an Aβ42-activated microglia-conditioned medium to induce A1 astrocytic activation in vitro.
- Assessed the impact of MFG-E8 on A1/A2 astrocytic balance.
- Investigated the molecular pathways involved: nuclear factor-κB (NF-κB) and PI3K-Akt signaling.
Main Results:
- Induced A1 astrocytic activation using Aβ42-activated microglia-conditioned medium.
- Demonstrated that MFG-E8 downregulates NF-κB and upregulates PI3K-Akt signaling.
- Showed that MFG-E8 suppresses the activation of detrimental A1 astrocytes.
Conclusions:
- MFG-E8 plays a regulatory role in modulating A1/A2 astrocytic balance.
- MFG-E8 exhibits neuroprotective properties by suppressing A1 astrocyte activation.
- MFG-E8 holds significant therapeutic potential for treating Alzheimer's disease.
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