Journal
REDOX BIOLOGY
Volume 17, Issue -, Pages 423-431Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2018.05.009
Keywords
24-hydroxycholesterol; Sirtuin 1; Tau; Oxysterols; Alzheimer's disease
Categories
Funding
- Compagnia di San Paolo [CSTO167048]
- University of Turin [RILO2016]
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It is now established that cholesterol oxidation products (oxysterols) are involved in several events underlying Alzheimer's disease (AD) pathogenesis. Of note, certain oxysterols cause neuron dysfunction and degeneration but, recently, some of them have been shown also to have neuroprotective effects. The present study, which aimed to understand the potential effects of 24-hydroxycholesterol (24-OH) against the intraneuronal accumulation of hyperphosphorylated tau protein, stressed these latter effects. A beneficial effect of 24-OH was demonstrated in SK-N-BE neuroblastoma cells, and is due to its ability to modulate the deacetylase sirtuin 1 (SIRT1), which contributes to preventing the neurotoxic accumulation of the hyperphosphorylated tau protein. Unlike 24-OH, 7-ketocholesterol (7 K) did not modulate the SIRT1-dependent neuroprotective pathway. To confirm the neuroprotective role of 24-OH, in vivo experiments were run on mice that express human tau without spontaneously developing tau pathology (hTau mice), by means of the intracerebroventricular injection of 24-OH. 24-OH, unlike 7 K, was found to completely prevent the hyperphosphorylation of tau induced by amyloid beta monomers. These data highlight the importance of preventing the loss of 24-OH in the brain, and of maintaining high levels of the enzyme SIRT1, in order to counteract neurodegeneration. [GRAPHICS] .
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