Involvement of p38 MAPK in Synaptic Function and Dysfunction

Int J Mol Sci. 2020 Aug 6;21(16):5624. doi: 10.3390/ijms21165624.

Abstract

Many studies have revealed a central role of p38 MAPK in neuronal plasticity and the regulation of long-term changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). However, p38 MAPK is classically known as a responsive element to stress stimuli, including neuroinflammation. Specific to the pathophysiology of Alzheimer's disease (AD), several studies have shown that the p38 MAPK cascade is activated either in response to the Aβ peptide or in the presence of tauopathies. Here, we describe the role of p38 MAPK in the regulation of synaptic plasticity and its implication in an animal model of neurodegeneration. In particular, recent evidence suggests the p38 MAPK α isoform as a potential neurotherapeutic target, and specific inhibitors have been developed and have proven to be effective in ameliorating synaptic and memory deficits in AD mouse models.

Keywords: Alzheimer’s disease; Tau; neuroinflammation; p38-MAPK α inhibitor; synaptic plasticity; β-amyloid.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / pathology
  • Humans
  • Inflammation / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Small Molecule Libraries / pharmacology
  • Synapses / drug effects
  • Synapses / enzymology*
  • Synapses / pathology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Small Molecule Libraries
  • p38 Mitogen-Activated Protein Kinases