The p38 map kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the CNS

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151 Scopus citations

Abstract

Inflammation in the central nervous system (CNS) is a common feature of age-related neurodegenerative diseases. Proinflammatory cytokines, such as IL-1β and TNFα, are produced primarily by cells of the innate immune system, namely microglia in the CNS, and are believed to contribute to the neuronal damage seen in the disease. The p38 mitogen-activated protein kinase (MAPK) is one of the kinase pathways that regulate the production of IL-1β and TNFα. Importantly, small molecule inhibitors of the p38 MAPK family have been developed and show efficacy in blocking the production of IL-1β and TNFα. The p38 family consists of at least four isoforms (p38α, β, γ, δ) encoded by separate genes. Recent studies have begun to demonstrate unique functions of the different isoforms, with p38α being implicated as the key isoform involved in CNS inflammation. Interestingly, there is also emerging evidence that two downstream substrates of p38 may have opposing roles, with MK2 being pro-inflammatory and MSK1/2 being antiinflammatory. This review discusses the properties, function and regulation of the p38 MAPK family as it relates to cytokine production in the CNS.

Original languageEnglish
Pages (from-to)199-211
Number of pages13
JournalAging and Disease
Volume1
Issue number3
StatePublished - 2010

Keywords

  • Microglia
  • Neurodegeneration
  • Neuroinflammation
  • Protein kinase
  • Signal transduction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

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