Integrin CD11b mediates α-synuclein-induced activation of NADPH oxidase through a Rho-dependent pathway
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The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin α M β 2 , but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b -/- microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47 phox and superoxide production. Mechanistically, α-synuclein bound to CD11b and subsequently activated Rho signaling pathway. α-Synuclein induced activation of RhoA and downstream ROCK but not Rac1 in a CD11b-dependent manner. Moreover, siRNA-mediated knockdown of RhoA impeded NOX2 activation in response to α-synuclein. Furthermore, we found that inhibition of NOX2 failed to interfere with the activation of RhoA signaling and interactions between α-synuclein and CD11b, further confirming that NOX2 was the downstream target of CD11b. Finally, we found that genetic deletion of CD11b abrogated α-synuclein-induced NOX2 activatoin in vivo . Taken together, our results indicated that integrin CD11b mediates α-synuclein-induced NOX2 activation through a RhoA-dependent pathway, providing not only a novel mechanistic insight but also a new potential therapeutic target for synucleinopathies.
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Extracellular α-synuclein induces microglial ROS production through CD11b integrin-mediated NOX activation via RhoA.
“With respect to microglial activation and neuroinflammation in PD, extracellular α-synuclein has been found to induce microglial ROS production through CD11b integrin-mediated NOX activation via RhoA [176].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [176]
α-Syn has been shown to increase the expression of COX-2 and the activity of microglial NADPH oxidase via CD11b.
“Moreover, α-Syn has been shown to increase the expression of COX-2 [116] and the activity of microglial NADPH oxidase via CD11b [117].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [117]
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- Authors
- Hou, L., Bao, X., Zang, C., Yang, H., Sun, F., Che, Y., Wu, X., Li, S., Zhang, D., & Wang, Q.
- Affiliations
- Dalian Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Zhang, Dan
- Wang, Qingshan
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 14
- Pages
- 600-608
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5975218
- OpenAlex
- W2767563688
- Cited by
- 98
- References
- 45
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 19 · 2023: 10 · 2022: 15 · 2021: 17 · 2020: 11 · 2019: 8 · 2018: 4
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Meteorological Sciences (2016-I2M-3–011)
- Dalian Medical University (201122)
- National Natural Science Foundation of China (81703264, 81630097, 81773718)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- CD11b, Mac-1, alpha-synuclein, NADPH oxidase NOX2, RhoA signaling, rocks, microglial activation, superoxide production, p47phox translocation, Parkinson's disease, synucleinopathies, TLR2
- MeSH terms
- NADPH Oxidase 2, Animals, Cells, Cultured, Humans, Inflammation, Male, Mice, Inbred C57BL, Signal Transduction, Microglia, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, CD11b Antigen, Mice, alpha-Synuclein
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