Interferon-beta (IFN-beta) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-beta on the central nervous system (CNS) are not well understood. To determine whether IFN-beta has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-beta and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN alpha/beta receptor (IFNAR). In response to IFN-beta treatment, no effect was observed on differentiation or proliferation. However, IFN-beta treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-beta treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-beta can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors. (C) 2009 Elsevier Inc. All rights reserved.