Benzene metabolite catechol promotes microglia-mediated neuroinflammation in Alzheimer’s disease via regulating NF-κB signaling
4 affiliations
- 1Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
- 2Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- 3Department of Preventive Medicine, School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Corresponding authors.
- 4Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Corresponding authors.
Abstract
Benzene is an occupational and environmental toxicant, and its exposure is associated with increased risk of Alzheimer’s disease (AD), yet its underlying mechanisms, particularly the roles of benzene metabolites, have not been elucidated. Here, benzene and its major metabolites were systematically evaluated through physicochemical characterization, blood–brain barrier permeability prediction, target identification, and pathway enrichment analysis. Single-nucleus RNA sequencing data were further analyzed using pathway activity scoring approaches to assess cell-type-specific signaling patterns. Molecular docking and molecular dynamics simulations were performed to explore interactions between selected metabolites and key regulatory proteins, and in vitro experiments were conducted for validation. Among the analyzed compounds, catechol was prioritized based on its predicted central nervous system accessibility and strong association with AD-related pathways. Pathway enrichment and transcriptomic scoring consistently highlighted NF-κB signaling as a key pathway, with preferential activation in microglia. Mechanistically, RELA (p65), a central regulator of NF-κB signaling, was identified as a potential target, and structural as well as experimental analyses supported the interaction between catechol and p65. Functional validation demonstrated that catechol enhanced Aβ-induced microglial activation and inflammatory responses. Collectively, these findings suggest that catechol may act as a critical mediator linking benzene exposure to microglia-driven neuroinflammation in AD, providing mechanistic insight into the contribution of environmental pollutants to neurodegenerative disease progression.
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BibTeX
@article{xu2026benzene,
title = {{Benzene metabolite catechol promotes microglia-mediated neuroinflammation in Alzheimer’s disease via regulating NF-κB signaling}},
author = {Zongtang Xu and Linpei Zhuo and Xiaoou Lin and Kun Xiang and Yao Yang and Conghui Dai and Jiaming Liu and Jing Sun},
journal = {Ecotoxicology and Environmental Safety},
year = {2026},
month = oct,
doi = {10.1016/j.ecoenv.2026.120946},
url = {https://doi.org/10.1016/j.ecoenv.2026.120946},
note = {CC BY},
}
RIS
TY - JOUR
TI - Benzene metabolite catechol promotes microglia-mediated neuroinflammation in Alzheimer’s disease via regulating NF-κB signaling
AU - Zongtang Xu
AU - Linpei Zhuo
AU - Xiaoou Lin
AU - Kun Xiang
AU - Yao Yang
AU - Conghui Dai
AU - Jiaming Liu
AU - Jing Sun
PY - 2026
DA - 2026/10/23
JO - Ecotoxicology and Environmental Safety
DO - 10.1016/j.ecoenv.2026.120946
UR - https://doi.org/10.1016/j.ecoenv.2026.120946
AB - Benzene is an occupational and environmental toxicant, and its exposure is associated with increased risk of Alzheimer’s disease (AD), yet its underlying mechanisms, particularly the roles of benzene metabolites, have not been elucidated. Here, benzene and its major metabolites were systematically evaluated through physicochemical characterization, blood–brain barrier permeability prediction, target identification, and pathway enrichment analysis. Single-nucleus RNA sequencing data were further analyzed using pathway activity scoring approaches to assess cell-type-specific signaling patterns. Molecular docking and molecular dynamics simulations were performed to explore interactions between selected metabolites and key regulatory proteins, and in vitro experiments were conducted for validation. Among the analyzed compounds, catechol was prioritized based on its predicted central nervous system accessibility and strong association with AD-related pathways. Pathway enrichment and transcriptomic scoring consistently highlighted NF-κB signaling as a key pathway, with preferential activation in microglia. Mechanistically, RELA (p65), a central regulator of NF-κB signaling, was identified as a potential target, and structural as well as experimental analyses supported the interaction between catechol and p65. Functional validation demonstrated that catechol enhanced Aβ-induced microglial activation and inflammatory responses. Collectively, these findings suggest that catechol may act as a critical mediator linking benzene exposure to microglia-driven neuroinflammation in AD, providing mechanistic insight into the contribution of environmental pollutants to neurodegenerative disease progression.
SN - 0147-6513
SN - 1090-2414
ER -