Alarmins and c-Jun N-Terminal Kinase (JNK) Signaling in Neuroinflammation

Nina D. Anfinogenova, Mark T. Quinn, Igor A. Schepetkin, Dmitriy N. Atochin

Research output: Contribution to journalReview articlepeer-review

Abstract

Neuroinflammation is involved in the progression or secondary injury of multiple brain conditions, including stroke and neurodegenerative diseases. Alarmins, also known as damage-associated molecular patterns, are released in the presence of neuroinflammation and in the acute phase of ischemia. Defensins, cathelicidin, high-mobility group box protein 1, S100 proteins, heat shock proteins, nucleic acids, histones, nucleosomes, and monosodium urate microcrystals are thought to be alarmins. They are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors. Being principal sterile inflammation triggering agents, alarmins are considered biomarkers and therapeutic targets. They are recognized by host cells and prime the innate immune system toward cell death and distress. In stroke, alarmins act as mediators initiating the inflammatory response after the release from the cellular components of the infarct core and penumbra. Increased c-Jun N-terminal kinase (JNK) phosphorylation may be involved in the mechanism of stress-induced release of alarmins. Putative crosstalk between the alarmin-associated pathways and JNK signaling seems to be inherently interwoven. This review outlines the role of alarmins/JNK-signaling in cerebral neurovascular inflammation and summarizes the complex response of cells to alarmins. Emerging anti-JNK and anti-alarmin drug treatment strategies are discussed.

Original languageEnglish
JournalCells
Volume9
Issue number11
DOIs
Publication statusPublished - 24 Oct 2020

Keywords

  • alarmin
  • Alzheimer’s disease
  • BAG family molecular chaperone regulator 3
  • c-Jun N-terminal kinase
  • high-mobility group box protein 1
  • microglia
  • neuroinflammation

ASJC Scopus subject areas

  • Medicine(all)

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