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Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ(1–42) and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells

[Image: see text] Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insul...

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Detalles Bibliográficos
Autores principales: Abascal, Maria Luisa, Sanjuan, Javier, Moyano, Paula, Sola, Emma, Flores, Andrea, Garcia, José Manuel, Garcia, Jimena, Frejo, María Teresa, del Pino, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768806/
https://www.ncbi.nlm.nih.gov/pubmed/36394833
http://dx.doi.org/10.1021/acs.chemrestox.2c00278
Descripción
Sumario:[Image: see text] Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aβ(1–42) and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3β (p-GSK3β; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction.