Aldose reductase inhibitors attenuate β-amyloid-induced TNF-α production in microlgia via ROS-PKC-mediated NF-κB and MAPK pathways
Abstract
Microglia-mediated neuroinflammation is a key risk factor to the development of Alzheimer' disease (AD). Aldose reductase (AR) has been found to be widely involved in inflammation-related diseases; however, whether aldose reductase inhibitors (ARIs) could be used to treat neuroinflammation is rarely reported. This study aims to evaluate the anti-neuroinflammatory effects of two major ARIs of Sorbinil (Sor) and Zopolrestat (Zol) in β-amyloid protein (Aβ)-induced microglia (BV-2). We find that Sor and Zol significantly inhibit TNF-α, IL-1β, IL-6 production from microglia in response to Aβ stimulation. Mechanism study showed that Sor and Zol decreased the production of intracellular ROS which resulted in an effective inhibition on the phosphorylation of several protein kinase C (PKC) isoforms including PKCα/β, δ, ζ/λ and mu. Moreover, Sor and Zol inactivated PCK-associated IKKβ-IκB-NF-κB and mitogen-activated protein kinase (JNK, p38, ERK) inflammation pathways. In summary, our findings suggest that Sor and Zol could inhibit Aβ-induced neuroinflammation by regulating ROS/PKC-dependent NF-κB and MAPK signaling pathways, indicating that ARIs could be promising agents for treating inflammation-related neurodegenerative diseases such as AD.
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PKC isozymes are involved in the pro-inflammatory response mediated by macrophages and microglia through activation of the NF-κB inflammation pathway.
“PKC isozymes are involved in the pro-inflammatory response mediated by macrophages [103] and, more recently, microglia [104] through activation of the NF-κB inflammation pathway.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [104]
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- Authors
- Song, X.-M., Yu, Q., Dong, X., Yang, H. O., Zeng, K.-W., Li, J., & Tu, P.-F.
- Affiliations
- Peking University (CN)
- Korea Institute of Science and Technology (KR)
- Corresponding author
- Zeng, Ke-Wu
- Li, Jun
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 50
- Pages
- 30-37
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W2625777374
- Cited by
- 60
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 4 · 2018: 12
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Science and Technology (44321012010)
- National Natural Science Foundation of China (81303253)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- aldose reductase inhibitors, sorbinil, zopolrestat, amyloid-beta, microglia, neuroinflammation, Alzheimer's disease, TNF-α, reactive oxygen species, protein kinase C, NF-κB signaling, MAPK signaling, IL-1β, interleukin-6, BV-2 cells
- MeSH terms
- Aldehyde Reductase, Alzheimer Disease, Animals, Cell Line, Phthalazines, Protein Kinase C, Risk Factors, Cytokines, Amyloid beta-Peptides, NF-kappa B, Reactive Oxygen Species, Microglia, Inflammation Mediators, Neurogenic Inflammation, MAP Kinase Signaling System, Imidazolidines, Mice, Benzothiazoles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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