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.
Fang et al (2021) An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke. Sci Transl Med. 13(597) eabb6716 PMID: 34108252