The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. has number of targets for phosphorylation, including MAPK-activated 2 (MK2). MK2 functions as master regulator RNA-binding proteins, indirectly controlling gene expression at the level translation. The role in regulating synthesis pro-inflammatory cytokines downstream inflammation and cellular well-described. A significant amount evidence, however, now points MAPK -MK2 signaling axis mediating synaptic plasticity through control AMPA receptor trafficking morphology dendritic spines. These processes are mediated cytoskeletal dynamics via activation cofilin-1 possibly Arc/Arg3.1. There evidence necessary group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption this may play an important cognitive dysfunction neurological disorders such fragile X syndrome Alzheimer’s disease. To date, neuronal response inflammatory stimuli not yet been investigated. In immune cells, it clear phosphorylated following broad range cell surface other mediators. We propose be player link between states dysregulation underlying functions. Finally, we discuss potential target therapeutic intervention disorders.