CIRP: New Horizons for CNS Injury Biomarkers and Therapy

Abstract Cold-inducible RNA-binding protein (CIRP) is a stress-response protein that protects cells under conditions of low temperature and other stresses. The expression of CIRP is induced by various stressors. CIRP regulates gene expression through complex, multi-layered mechanisms and plays a central role in physiological and pathological processes, including cell proliferation, apoptosis, inflammatory responses, and circadian rhythms. In central nervous system (CNS) injuries, CIRP exhibits a dual role. Intracellular CIRP has a neuroprotective function. In contrast, when released into the extracellular space as eCIRP, it acts as a damage-associated molecular pattern (DAMP) that exacerbates neuroinflammation. Serum levels of eCIRP are significantly elevated in patients with CNS injuries, such as acute ischemic stroke and intracerebral hemorrhage, suggesting its potential as a biomarker for diagnosis and prognosis. Furthermore, targeting the eCIRP signaling pathway has shown significant therapeutic effects in various models of neurological injury. Strategies include using inhibitory peptides like C23 and M3, as well as microRNA-based approaches. Here, we systematically review the molecular characteristics, expression regulation, and biological functions of CIRP, with a focus on its neuroprotective role, biomarker potential, and therapeutic targeting in CNS injuries.