Fig. 3. Pharmacological modulation of the ISR as a therapeutic approach in ischemic disease.
Various therapeutic strategies have been developed to intervene the ISR. PERK inhibitors can relieve the unfolded protein response (UPR) and the ISR. Acute activation of PERK may activate the ISR and protect cells from reperfusion injury. Dephosphorylation of eIF2α may be targeted to either enhance or attenuate the ISR for therapeutic gain.