TAK1 inhibition for treatment of cerebral ischemia

Abstract

TGFβ-activated kinase 1 (TAK1), a MAP3 kinase, is involved in at least five signaling cascades that modulate ischemic brain damage. Inhibition of TAK1 may therefore be an efficient way to interfere with multiple mechanisms in ischemic stroke. Indeed, a recent publication in Experimental Neurology confirmed that TAK1 inhibition by 5Z-7-oxozeaenol is neuroprotective. The beneficial effect of 5Z-7-oxozeaenol was associated with a reduced activation of Jun kinase that leads to inflammation and apoptosis. Recently, other TAK1 inhibitors were developed suggesting that TAK1 may prove as an efficient therapeutic target for neurodegenerative diseases if safety issues are not limiting.