Tat-CIRP is a peptide derived from the high affinity binding region of cold-inducible RNA binding protein (CIRP) which competitively binds to myeloid differentiation factor 2 (MD2) and blocks the MD2-CIRP interaction. MD2 is an essential accessory protein for Toll like receptor 4 (TLR4) activation and blocking the function of MD2 and TLR4 with Tat-CIRP is neuroprotective, reducing apoptosis and necroptosis in vitro. In vivo, Tat-CIRP is neuroprotective against ischemic and hemorrhagic stroke in mice and reduces brain infarct volume and preserves neurological function in rhesus monkeys 30 days after ischemic stroke.
