The novel calpain inhibitor A-705253 prevents stress-induced tau hyperphosphorylation in vitro and in vivo

► Calpain inhibitor A-705253 examined in acute models of tau hyperphosphorylation. ► A-705253 blocked in vitro low temperature-induced tau phosphorylation in hippocampal slices. ► A-705253 blocked in vivo stress-induced tau hyperphosphorylation in mice. ► A-705253 decreased expression of the calpain proteolytic p25 fragment.