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Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer's disease both in vitro and in population-based data

L. Saveleva, T. Cervena, C. Mengoni, M. Sima, Z. Krejcik, K. Vrbova, J. Sikorova, L. Mussalo, TOE. de Crom, Z. Šímová, M. Ivanova, MA. Shahbaz, E. Penttilä, H. Löppönen, AM. Koivisto, MA. Ikram, PI. Jalava, T. Malm, S. Chew, M. Vojtisek-Lom, J....

. 2024 ; 20 (12) : 8825-8843. [pub] 20241123

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003145

Grantová podpora
JPND2019-466-037 ADAIR project
22-10279S Czech Science Foundation
Ministry of Education, Youth, and Sports of the Czech Republic
CZ.02.1.01/0.0/0.0/16_013/0001821 European Union-European Structural and Investments Funds in the frame of Operational Programme Research Development and Education
Doctoral Program in Molecular Medicine at the University of Eastern Finland
Kuopio University Foundation,
65231471 North Savo Regional Fund of the Finnish Cultural Foundation
97030.2021.101.430/057/RB Stichting Erasmus Trustfonds
733051107 Netherlands Organisation for Health Research and Development
n/a Pohjois-Savon Rahasto
JPND2019-466-037 EU Joint Programme - Neurodegenerative Disease Research

INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.

Citace poskytuje Crossref.org

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