The present invention relates to a novel method for the treatment and/or prophylaxis of a tau-mediated neurodegenerative disease and/or of a tau-mediated neurodegenerative pathological condition, especially of a neurodegenerative disease and/or of a neurodegenerative pathological condition associated with and/or accompanied by tau aggregation, and in particular for the treatment and/or prophylaxis of a tauopathy compounds and/or agents and compositions for such treatment and/or prophylaxis, and the manufacture of the compounds and/or agents and compositions suitable for the said treatment and/or prophylaxis. In this regard, the present invention relates especially to the use of compounds acting as PERK activator, a prodrug thereof, a derivative thereof and/or a pharmaceutically acceptable salt of any thereof, as a medicament. In contrast to the prior art which addresses mainly PERK inhibition, or occasionally only the apoptotic arm of PERK of activation, the present invention pertains to the effects of indirect or direct PERK activation achieved via the neuroprotective arm of PERK signaling.