Roles of Extracellular Regulated Kinase 1/2 (ERK 1/2), Including form Activated by BDNF/TrkB, and Their Contribution in Neurodegenerative Diseases

Brain-derived growth factor, BDNF, has critical roles in a wide variety of neuronal aspects, including cell survival, differentiation, and synaptic function after their maturation. TrkB, a high affinity receptor for BDNF, is a major contributor in these neuronal aspects, and its functions are exerted via stimulating intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways. Especially, extracellular regulated kinase 1/2 (ERK 1/2), a major serine-threonine kinase and belonging to MAPK family, also works as a downstream molecule after activation of BDNF/TrkB system. Interestingly, growing evidence has demonstrated that ERK1/2 signaling exerts positive or negative influence on neurons in both healthy and pathological conditions in the central nervous system (CNS). Indeed, activation of ERK 1/2 stimulated by the BDNF/TrkB system is involved in regulation of synaptic plasticity. On the other hand, over-activation of ERK1/2 signaling under the pathological conditions is closely related to the neurodegeneration. In this review, we show how ERK1/2 signaling affects neuronal fate, including cell survival or cell death, in the CNS. Moreover, we discuss the involvement of overactivation of ERK signaling in the neurodegeneration observed in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington’s disease (HD).