A novel role for Kv1.3 blockers: protecting neural progenitor cells from a hostile inflammatory environment.

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see Review of Wang et al. Multiple sclerosis (MS) is a debilitating neurological disorder that affects ϳ2.5 million individuals worldwide. While the precise etiology of the disease is unknown, both immune-mediated inflammation and neurodegeneration play a role in disease progression. Myelin-specific activated T-cells infiltrate the CNS and perpetuate inflammation that causes damage to the myelin sheath of axons, ultimately leading to axonal transection and loss. As the disease progresses, there is increased gray matter involvement and brain atrophy , despite a reduction in inflammation. Currently, there are six Food and Drug Administration-approved immu-nomodulatory therapies that reduce new inflammatory lesions and clinical exacer-bations; however, these therapies become less effective as the disease progresses. Thus, there is a need for novel neuropro-tective and neurorestorative therapies for individuals with MS. Neural progenitor cells (NPCs) are multipotent cells found in the adult CNS with the ability to migrate, proliferate, and differentiate into both neurons and glial cells. Based on these properties, there is much interest in using NPCs for therapeutic purposes in neurological diseases such as MS. Although endogenous NPCs can promote functional recovery early in disease through remyelination, they have proven to be of limited benefit in chronic CNS inflammation due to impaired neu-rogenesis (Pluchino et al., 2008). However , exogenous transplantation of NPCs has shown benefit in a murine model for MS, experimental autoimmune encepha-lomyelitis (EAE), most likely through mechanisms other than simple cell replacement (Pluchino et al., 2005). NPCs reduce inflammation and promote remy-elination by releasing neurotrophic factors (brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and ciliary neurotrophic factor) and im-munoregulatory cytokines (transforming growth factor-␤) at lesion sites. Despite these benefits, little evidence has been found that NPCs differentiate into neuro-nal cells and aid in tissue regeneration in vivo. One possible barrier is that the in-flammatory CNS microenvironment established by myelin-specific CD4ϩ and CD8ϩ T-cells inhibits NPC neurogenesis. Thus, to successfully implement NPCs as a therapeutic option, researchers must induce NPCs to overcome the unfavorable microenvironment and drive tissue regeneration. A recently published study by Wang et al. (2010) examined the interaction between NPCs and activated CD8ϩ T-cells. Using human NPCs …