GAP-43 Protein and Its Proteolytic Fragment in Spinal Cord Cells in Rats with Experimental Allergic Encephalomyelitis

Abstract

The limited regenerative capacity of the central nervous system (CNS) is one of the key factors promoting the development of neurodegenerative diseases, including multiple sclerosis. The regenerative potential of CNS cells can be evaluated in terms of the level of GAP-43 protein, which is involved in the processes of neuritogenesis and growth cone navigation. Cleavage of GAP-43 by m-calpain to form the fragment GAP-43-3, which lacks 40 N-terminal amino acids, probably leads to loss of the initial functions of the protein, which may have adverse influences on the regenerative potential of the CNS. The present study was performed on the most appropriate model of multiple sclerosis – experimental allergic encephalomyelitis (EAE) in rats. The spinal cord of animals with EAE was shown to have inflammatory infiltrates and deformed motoneurons; limb pareses and paralysis developed. When EAE was mild, about 60% of GAP-43 in rat spinal cord cells was present in the form of GAP-43-3. In severe forms of EAE, with tetraplegia, the extent of GAP-43 proteolysis by calpain reached 85%. In this situation, GAP-43-3 was found mainly in microglial cells. We suggest that during the development of EAE, proteolytic cleavage of GAP-43 protein by m-calpain to form GAP-43-3 can significantly alter its properties, suppressing the regenerative ability of CNS cells and exacerbating the course of the pathological process.