Fas(t) track to apoptosis in MS: TNF receptors may suppress or potentiate CNS demyelination.

Abstract

Molecules of the tumor necrosis factor (TNF) receptor superfamily could both suppress and promote MS disease activity. These molecules, including Fas (CD95), TRAIL receptor 2 (TRAIL R2), and TNF receptors p55 and p75, contain a “death sequence” in their cytoplasmic tail linking them to caspases—a series of potentially destructive cysteine proteases. Signaling activates a caspase cascade, culminating in the fragmentation of nuclear DNA and ultimately, self-destruction by programmed cell death or “apoptosis.” MS remissions could be triggered by the elimination of CNS-infiltrating inflammatory cells through Fas, TRAIL R2, or TNF p55/p75 receptor pathways. Conversely, MS exacerbations could result from the killing of oligodendrocytes via stimulation through Fas receptors. The articles by Huang et al.1 and Comi et al.2 in this issue of Neurology support a role for TNF family receptors in the regulation of …