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Author Spotlight: Insight Into Advances in Prion Diseases Research
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Author Spotlight: Insight Into Advances in Prion Diseases Research

Published on: August 11, 2023

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Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells

Valentina Villa1, Stefano Thellung1, Alessandro Corsaro1

  • 1Laboratory of Pharmacology, Dept. of Internal Medicine, and Center of Excellence for Biomedical Research (CEBR), University of Genova, 16132, Genoa, Italy.

Molecular Neurobiology
|November 19, 2014
PubMed

Insights

Prion protein fragments activate microglia, releasing inflammatory mediators that harm neurons. COX2 inhibitors, like celecoxib, can block this activation, offering a potential therapeutic strategy for prion diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglia activation is key in prion encephalopathies' inflammatory response.
  • Prion protein fragments (PrP90-231) model neurotoxic prion activity.

Purpose of the Study:

  • Investigate PrP90-231's effect on microglia activation in vitro.
  • Determine the role of cyclooxygenase (COX) activity in PrP90-231-induced neuroinflammation.
  • Evaluate COX inhibitors as a potential therapeutic approach for prion diseases.

Main Methods:

  • Primary microglia and N9 microglial cells were treated with PrP90-231.
  • Assessed cell proliferation, prostaglandin E2 (PGE2), and nitric oxide (NO) release.
  • Tested the effects of ketoprofen (COX1 inhibitor) and celecoxib (COX2 inhibitor) on microglial activation.

Main Results:

  • PrP90-231 induced microglial proliferation arrest and released PGE2 and NO.
  • Conditioned medium from treated microglia was toxic to A1 mesencephalic neurons.
  • Celecoxib significantly reverted PrP90-231-induced microglial activation, while ketoprofen did not.

Conclusions:

  • Microglia play a critical role in prion disease neurotoxicity.
  • PrP90-231-induced neuroinflammation is largely mediated by COX2 activation.
  • COX2-selective inhibitors show potential as adjunctive therapies against prion disease neuroinflammation.
Keywords:
CelecoxibCyclooxygenaseMicrogliaNitric oxide synthasePrP90-231Prion diseases

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