Editors' ChoiceNeurobiology

EPO on the Brain

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Science's STKE  14 Aug 2001:
Vol. 2001, Issue 95, pp. tw1
DOI: 10.1126/stke.2001.95.tw1

Neuronal apoptosis can be triggered by factors such as exposure to excitotoxins and free radicals. One way that the brain can avoid such stress-induced damage is to produce erythropoietin (EPO), a cytokine more commonly associated with hematopoiesis. Digicaylioglu and Lipton report that rat brain neurons do express receptors for EPO, which when stimulated, can activate the kinase Jak2. This initial signal transduction event has been well-characterized in nonneuronal cells. However, in brain cells, Jak2 seems to activate a new downstream target, the tanscription factor NF-κB. EPO treatment of neurons caused the nuclear translocation of NF-κB and a sustained increase in NF-κB association with DNA. The neuroprotective effects of EPO were abolished when Jak2 or NF-κB action was inhibited. The authors propose that Jak2 may phosphorylate IκBα, a modification that would free NF-κB from inhibition. Because NF-κB regulates the expression of antiapoptotic proteins, the proposed EPO receptor-Jak2-NF-κB signaling pathway may be a critical component of preventing neuronal cell death.

M. Digicaylioglu, S.A. Lipton, Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades. Nature 412, 641-647 (2001). [Online Journal]

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