Calcitonin gene-related peptide (CGRP): A potential therapeutic target against sepsis and sepsis-associated multiple...

Sepsis, a leading cause of death in intensive care units, is a systemic reaction to infections that causes significant organ damage and necessitates new treatments. Calcitonin gene-related peptide (CGRP) has been identified as a key target in sepsis experimental research. CGRP, a 37 amino acid neuropeptide found throughout the body, plays a beneficial role in sepsis by reducing inflammatory cytokine release, inhibiting the oxidative stress pathway, and decreasing organ-specific inflammation. Research evidence on knockout mice states that specific receptor deficient mice [CGRP receptor activity-modifying protein (RAMP1) and transient receptor potential vanilloid 1 (TRPV1)] exhibited more pronounced neutrophil aggregation and inflammation compared to wild-type mice, suggesting that a CGRP agonism could be a promising treatment for sepsis. Further, CGRP modulates many specific signaling pathways to protect against sepsis-induced multiple organ damage. The present review includes key aspects of CGRP and in-vitro and in-vivo evidence regarding the prevailing contribution of CGRP neuropeptide in ameliorating sepsis-associated organ dysfunction. This study emphasizes the mechanistic insights into the beneficial effects of CGRP on sepsis-associated organ damage. This current review is the first to compile the effects of CGRP in improving sepsis-induced organ dysfunction and underscores its potential as a therapeutic target for organ-specific damage caused by sepsis.