24S-hydroxycholesterol induces inflammatory gene expression in primary human neural cells

Piotr Alexandrov, Jian Guo Cui, Yuhai Zhao, Walter J. Lukiw

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

24S-hydroxycholesterol, the primary oxidation product of cholesterol in the brain, plays a key role in cholesterol elimination and homeostasis. While the concentration of this neurotoxic oxysterol decreases with age, 24S-hydroxycholesterol is elevated in Alzheimer's disease. In this study, we examined the effects of 24S-hydroxycholesterol on gene expression in human neural cells, a primary coculture of neurons and glia useful for studying pathogenic mechanisms in Alzheimer's disease. DNA array and Western analysis revealed elevations in the expression of a pro-inflammatory gene family that included β-amyloid precursor protein, cyclooxygenase-2, cytosolic phospholipase A2 and heat shock protein 70, an effect that was partially suppressed by simvastatin. These data indicate that cholesterol oxides induce atypical gene expression in neural cells that may contribute to the etiology or pathogenesis of inflammatory brain disease.

Original languageEnglish (US)
Pages (from-to)909-913
Number of pages5
JournalNeuroreport
Volume16
Issue number9
DOIs
StatePublished - Jun 21 2005

Keywords

  • 24S-hydroxycholesterol
  • Alzheimer's disease
  • Brain gene expression
  • Cholesterol
  • Inflammation
  • Simvastatin

ASJC Scopus subject areas

  • Neuroscience(all)

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