Distinct roles for ERK1 and ERK2 in pathophysiology of CNS

Mitogen-activated protein kinases ERK1 and ERK2 have been implicated in various pathophysiological events of the CNS, but their specific roles in cell processes under physiologic and pathological conditions remain to be determined. ERK1/2 was originally identified as a kinase activity that mediates neuronal survival and neuroprotection, but it was subsequently found that ERK1/2 also plays a critical role in neurodegeneration. This dichotomy makes it difficult to target ERK1/2 for neuroprotection. Accumulating evidence suggests that ERK1 and ERK2 may play distinct functions in a variety of cell fate decisions. In this review, I summarize recent evidence for distinct roles for individual ERK isoforms in pathophysiology of the CNS.