NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.

ABSTRACT:

Background

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.

Methodology

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 hippo

SUBMITTER: Lopez-Sampere Y 

PROVIDER: S-EPMC12907107 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature