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

Edward Beamer1, Sonia A L Corrêa1

  • 1Faculty of Science and Engineering, Department of Life Sciences, Manchester Metropolitan University Manchester, Manchester, United Kingdom.

Frontiers in Cell and Developmental Biology
|February 15, 2021
PubMed

Insights

The p38 mitogen-activated protein kinase (MAPK)-MAPK-activated protein kinase 2 (MK2) pathway regulates synaptic plasticity and may be crucial for cognitive function. This signaling axis is implicated in neurological disorders and offers therapeutic potential.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • p38 mitogen-activated protein kinase (MAPK) responds to stress and phosphorylates MAPK-activated protein kinase 2 (MK2).
  • MK2 regulates RNA-binding proteins, affecting gene expression at the translational level and is known to control pro-inflammatory cytokine synthesis.
  • Emerging evidence implicates the p38MAPK-MK2 axis in synaptic plasticity, influencing AMPA receptor trafficking and dendritic spine morphology.

Purpose of the Study:

  • To investigate the role of neuronal MK2 in mediating synaptic plasticity in response to inflammatory stimuli.
  • To explore the connection between inflammatory states, synaptic plasticity, and cognitive function via the p38MAPK-MK2 signaling pathway.
  • To discuss the therapeutic potential of targeting the p38MAPK-MK2 axis for neurological disorders.

Main Methods:

  • Review of existing literature on p38MAPK-MK2 signaling in immune and neuronal cells.
  • Analysis of MK2's role in cytoskeletal dynamics (cofilin-1) and gene expression (Arc/Arg3.1).
  • Examination of MK2's necessity in group I metabotropic glutamate receptors long-term depression (mGluR-LTD).

Main Results:

  • The p38MAPK-MK2 pathway is involved in synaptic plasticity through regulation of AMPA receptor trafficking and dendritic spine morphology.
  • MK2 is essential for mGluR-LTD and influences cytoskeletal dynamics and gene expression relevant to synaptic function.
  • Disruption of this signaling is linked to cognitive deficits in neurological conditions like fragile X syndrome and Alzheimer's disease.

Conclusions:

  • Neuronal MK2 is proposed as a key mediator linking inflammation to synaptic plasticity and cognitive dysfunction.
  • The p38MAPK-MK2 signaling pathway represents a potential therapeutic target for neurological disorders.
  • Further research is needed to elucidate the precise role of neuronal MK2 in inflammatory responses affecting synaptic plasticity.
Keywords:
AMPAR traffickingMK2cognitionhippocampusmGluR-LTDneuroinflammationp38MAPKsynaptic plasticity

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