B fragment of cholera toxin conjugated to saporin

Abstract

Saporin conjugates have proven extremely versatile and valuable in the selective destruction of a variety of cell types. In the nervous system, the use of saporin-conjugated toxins has generally been directed toward neurons. We were interested in whether saporin conjugates could be used to target other nervous tissue cell types, particularly the myelin-forming cells. Taking advantage of the fact that myelin is rich in GM1 ganglioside and that the B fragment of cholera toxin has a high affinity for GM1, we used a conjugate of the B fragment of cholera toxin and saporin (CTB-sap) to target myelin-producing cells (oligodendrocytes) in the central nervous system (CNS) (Fig. 1). We found that CTB-sap is effective in removing oligodendrocytes in addition to other glial cells and largely leaves neurons intact. We successfully used CTB-sap to study demyelination and remyelination in the spinal cord (1), and our preliminary results suggest that CTB-sap will be useful for inducing demyelinating lesions in other parts of the CNS. © 2005 Humana Press Inc.