An Overview on C-Terminal Agrin Fragment

Abstract

Agrin is a large heparan sulfate proteoglycan predominantly expressed in the nervous system and at the neuromuscular junction, where it plays a pivotal role in synapse formation and stabilization. The C-terminal agrin fragment (CAF) is a cleavage product generated by the proteolytic activity of neurotrypsin, a serine protease that cuts agrin at specific sites, producing fragments including the 22-kDa C-terminal portion known as CAF22. This fragment has gained attention as a potential circulating biomarker for muscle wasting, particularly in conditions such as sarcopenia, frailty, and chronic diseases including chronic kidney disease and heart failure. Elevated serum levels of CAF22 are believed to reflect increased muscle catabolism and neuromuscular degradation, correlating with physical decline and functional impairment. Its role as a non-invasive biomarker offers significant clinical relevance for early detection, risk stratification, and monitoring of therapeutic interventions in muscle-wasting disorders. Furthermore, research into CAF may contribute to a deeper understanding of the neuromuscular junction integrity and its role in systemic diseases.