期刊
JOURNAL OF NEUROSCIENCE
卷 30, 期 14, 页码 5020-5027出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0311-10.2010
关键词
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资金
- Maryland Stem Cell Fund
- National Multiple Sclerosis Society [TR 3760-A-3]
- National Institutes of Health [R01-NS056884, R01-NS41435]
There is a great need for pharmacological approaches to enhance neural progenitor cell (NPC) function particularly in neuroinflammatory diseases with failed neuroregeneration. In diseases such as multiple sclerosis and stroke, T-cell infiltration occurs in periventricular zones where NPCs are located and is associated with irreversible neuronal loss. We studied the effect of T-cell activation on NPC functions. NPC proliferation and neuronal differentiation were impaired by granzyme B(GrB) released by the T-cells. GrB mediated its effects by the activation of a Gi-protein-coupled receptor leading to decreased intracellular levels of cAMP and subsequent expression of the voltage-dependent potassium channel, Kv1.3. Importantly, blocking channel activity with margatoxin or blocking its expression reversed the inhibitory effects of GrB on NPCs. We have thus identified a novel pathway in neurogenesis. The increased expression of Kv1.3 in pathological conditions makes it a novel target for promoting neurorestoration.
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