Gamma subunit of complement component 8 is a neuroinflammation inhibitor
Jong-Heon Kim1, Ruqayya Afridi2, Jin Han2
1Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea.
Brain : a Journal of Neurology
|December 31, 2020
Summary
Complement component 8 gamma (C8G) inhibits neuroinflammation and cognitive decline in Alzheimer's disease models. Higher C8G levels in patients suggest a potential therapeutic target for neurological diseases.
Area of Science:
- Immunology
- Neuroscience
- Molecular Biology
Background:
- The complement system, part of innate immunity, typically promotes inflammation.
- Alzheimer's disease (AD) is characterized by significant neuroinflammation.
- The specific role of complement component 8 gamma (C8G) in neuroinflammation was previously unknown.
Purpose of the Study:
- To investigate the role of complement component 8 gamma (C8G) in neuroinflammation, particularly in the context of Alzheimer's disease.
- To explore C8G's potential as a therapeutic target for neuroinflammatory disorders.
Main Methods:
- Analysis of C8G levels in human Alzheimer's disease patient samples (brain tissue, CSF, plasma).
- Assessment of C8G expression in inflamed mouse brain models.
- In vivo and in vitro experiments using recombinant C8G protein and shRNA-mediated knockdown in animal models of AD.
- Identification of C8G interacting proteins using biochemical assays.
Main Results:
- Elevated C8G levels were observed in Alzheimer's disease patients and in inflamed mouse brains, primarily localized to astrocytes.
- C8G administration inhibited glial hyperactivation, neuroinflammation, and cognitive decline in AD animal models.
- Sphingosine-1-phosphate receptor 2 (S1PR2) was identified as a novel interaction partner of C8G.
- Astrocyte-derived C8G was shown to antagonize S1P-induced microglial activation via S1PR2.
Conclusions:
- Complement component 8 gamma (C8G) acts as a novel inhibitor of neuroinflammation.
- C8G plays a protective role against neuroinflammation and cognitive impairment in Alzheimer's disease.
- Targeting C8G presents a promising therapeutic strategy for Alzheimer's disease and related neurological conditions.
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