Overall, despite the tested Nrf2-pathway activators having shown a neuroprotective role against oxidative stress and tau phosphorylation triggered by annonacin, supporting a therapeutic potential of Nrf2-pathway activators in the context of tauopathies, our data suggest that these neuroprotective effects may not be exclusively related to the Nrf2 pathway. This evidence concerns the gene NFE2L2 and tauopathy.