Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ1–42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells

Abascal, Maria LuisaSanjuan, JavierMoyano-Cires Ivanoff, Paula VivianaSola Vendrell, EmmaFlores, AndreaGarcía Sánchez, José ManuelGarcía Lobo, JimenaFrejo Moya, María TeresaPino Sans, Javier Del2023-06-222023-06-222022-11-170893-228X10.1021/acs.chemrestox.2c00278https://hdl.handle.net/20.500.14352/72712CRUE-CSIC (Acuerdos Transformativos 2022)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 Aβ1–42 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.engAtribución 3.0 EspañaInsulin Signaling Disruption and INF-γ Upregulation Induce Aβ1–42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cellsjournal articlehttps://doi.org/10.1021/acs.chemrestox.2c00278open accessEndocrinologíaBiología celular (Biología)3205.02 Endocrinología2407 Biología Celular