biostudies-literatureLopez-Sampere YCarlos III Health InstituteFundación Ramón ArecesXarxa de Bancs de Tumors de Catalunya104068https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907107biostudies-literatureUnknown91<h4>Background</h4>Nuclear factor erythroid 2-related factor 2 (NRF2) regulates antioxidant defenses and protects against neurodegeneration, including Alzheimer's disease (AD). Its age-related decline disrupts redox balance and increases neuronal vulnerability, but the early hippocampal effects remain unclear. Here, we tested whether NRF2 loss affects tau seeding and spreading in a PHF-tau-inoculated mouse model, contributing to accelerated aging.<h4>Methodology</h4>Three-month-old NRF2-knockout (Nfe2l2^-/-) and wild-type (WT) mice received hippocampal inoculations of human AD-derived PHF-tau, and tau propagation was analyzed after three months. To elucidate the molecular underpinnings of the observed changes, we performed integrative phosphoproteotranscriptomic analyses of hippoRedox biologyNRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.PMC12907107PT20/00171PI23/00176CD23/00097PI20/000155Vinyals ADakterzada FDel Rio JARoca-Pereira SSantamaria ERomero LVela-Martinez MPortero-Otin MAndres-Benito PPinol-Ripoll GMato-Blanco XFerrer IFernandez-Irigoyen JSantpere GPovedano MMengod Soler PLopez-Sampere YfalseNRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.<h4>Background</h4>Nuclear factor erythroid 2-related factor 2 (NRF2) regulates antioxidant defenses and protects against neurodegeneration, including Alzheimer's disease (AD). Its age-related decline disrupts redox balance and increases neuronal vulnerability, but the early hippocampal effects remain unclear. Here, we tested whether NRF2 loss affects tau seeding and spreading in a PHF-tau-inoculated mouse model, contributing to accelerated aging.<h4>Methodology</h4>Three-month-old NRF2-knockout (Nfe2l2^-/-) and wild-type (WT) mice received hippocampal inoculations of human AD-derived PHF-tau, and tau propagation was analyzed after three months. To elucidate the molecular underpinnings of the observed changes, we performed integrative phosphoproteotranscriptomic analyses of hippo2026-01-01T00:00:00Z2026 Feb2026-07-15T21:30:11.849Z2026-07-09T10:13:58.831ZS-EPMC129071074165082210.1016/j.redox.2026.104068