Pterostilbene inhibits amyloid-β-induced neuroinflammation in a microglia cell line by inactivating the NLRP3/caspase-1 inflammasome pathway

J Cell Biochem. 2018 Aug;119(8):7053-7062. doi: 10.1002/jcb.27023. Epub 2018 May 8.

Abstract

Neuroinflammation has been known as an important pathogenetic contributor of Alzheimer's disease (AD). Pterostilbene is a natural compound which has neuroprotective activity. However, the effect of pterostilbene on amyloid-β (Aβ)-induced neuroinflammation has not been clarified. The aim of the present study was to investigate the effect of pterostilbene on Aβ-induced neuroinflammation in microglia. The results indicated that pterostilbene attenuated Aβ1-42 -induced cytotoxicity of BV-2 cells. Aβ1-42 induced NO production and iNOS mRNA and protein expression, while pterostilbene inhibited the induction. The expression and secretion levels of IL-6, IL-1β, and TNF-α were enhanced by Aβ1-42 treatment, whereas pterostilbene decreased them. Aβ1-42 activated NLRP3/caspase-1 inflammasome, which was inactivated by pterostilbene. In addition, the inhibitor of caspase-1 Z-YVAD-FMK attenuated the Aβ1-42 -induced neuroinflammation in BV-2 cells. In conclusion, pterostilbene attenuated the neuroinflammatory response induced by Aβ1-42 in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.

Keywords: Alzheimer's disease; NLRP3/caspase-1 inflammasome; neuroinflammation; pterostilbene.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism*
  • Caspase Inhibitors / pharmacology
  • Cell Line, Transformed
  • Inflammasomes / genetics
  • Inflammasomes / metabolism*
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Microglia
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Stilbenes / pharmacology*
  • Tosylphenylalanyl Chloromethyl Ketone / analogs & derivatives
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology

Substances

  • Amyloid beta-Peptides
  • Caspase Inhibitors
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Peptide Fragments
  • Stilbenes
  • amyloid beta-protein (1-42)
  • tyrosyl-valyl-alanyl-aspartic acid fluoromethyl ketone
  • pterostilbene
  • Tosylphenylalanyl Chloromethyl Ketone
  • Caspase 1