[Oligodendrocyte cell death by caspase family proteases]

Oligodendrocytes are myelin forming cells in mammalian central nervous system. About 50% of oligodendrocytes (OLGs) undergo cell death in normal development. In addition, massive OLG cell deaths have been observed in multiple sclerosis (MS). Tumor necrosis factor (TNF) is thought to be one of the mediators responsible for the damage of oligodendrocytes (OLGs). The addition of TNF-a to primary cultures of OLGs significantly decreased the number of live OLGs in 72 h. Chemical inhibitors Ac-YVAD-CHO (a specific inhibitor of caspase-1-like proteases) enhanced the survival of OLGs treated with TNF-a, indicating that caspase-1-mediated cell-death pathway are activated in TNF-induced OLG cell death, caspase-11 is involved in activation of caspase-1. Oligodendrocytes from CASP-11-deficient mice are partially resistant to TNF-induced cell death. These results suggest that the activation of caspases is crucial in TNF-induced OLG cell death and inhibition of caspase family may be a novel approach to treat neurodegenerative diseases such as MS.