download r@1n rebirth activator 1.7 final

The developed assay revealed to be sufficiently stable and robust to assess an activating EC 50-value. Instead of using PERK’s natural substrate proteins, eIF2α and NRF2, we applied SMAD3 as phosphorylation-accepting protein and successfully detected cell-free PERK activation and inhibition by selected modulators (e.g., calcineurin-B, GSK2606414). By applying the catalytic domain of recombinant human PERK, we initially determined ideal conditions of the kinase assay reaction, including parameters such as optimal kinase concentration, temperature, and reaction time. Our study aimed at the development of a cell-free screening assay enabling the detection of novel direct PERK activators. So far, a shortage of available direct PERK activators has been limiting the progresses in this field.

The activation of the unfolded protein response, particularly via the PERK pathway, has been suggested as a promising therapeutic approach in tauopathies, a group of neurodegenerative disorders characterized by the abnormal phosphorylation and aggregation of tau protein.

Download r@1n rebirth activator 1.7 final