New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death

Noriko Noguchi, Yasuomi Urano, Wakako Takabe, Yoshiro Saito

Research output: Contribution to journalReview articlepeer-review

29 Citations (Scopus)


24(S)-Hydroxycholesterol (24S-OHC), which is enzymatically produced in the brain, has been known to play an important role in maintaining cholesterol homeostasis in the brain and has been proposed as a possible biomarker of neurodegenerative disease. Recent studies have revealed diverse functions of 24S-OHC and gained increased attention. For example, 24S-OHC at sublethal concentrations has been found to induce an adaptive response via activation of the liver X receptor signaling pathway, thereby protecting neuronal cells against subsequent oxidative stress. It has also been found that physiological concentrations of 24S-OHC suppress amyloid-β production via downregulation of amyloid precursor protein trafficking in neuronal cells. On the other hand, high concentrations of 24S-OHC have been found to induce a type of nonapoptotic programmed cell death in neuronal cells expressing little caspase-8. Because neuronal cell death induced by 24S-OHC has been found to proceed by a unique mechanism, which is different from but in some ways similar to necroptosis - necroptosis being a type of programmed necrosis induced by tumor necrosis factor α - neuronal cell death induced by 24S-OHC has been called "necroptosis-like" cell death. 24S-OHC-induced cell death is dependent on the formation of 24S-OHC esters but not on oxidative stress. This review article discusses newly reported aspects of 24S-OHC in neuronal cell death and sheds light on the possible importance of controlling 24S-OHC levels in the brain for preventing neurodegenerative disease.

Original languageEnglish
Article number12496
Pages (from-to)366-372
Number of pages7
JournalFree Radical Biology and Medicine
Publication statusPublished - 2015 Oct 1


  • 24(S)-Hydroxycholesterol
  • CYP46A1
  • Cell death
  • Cholesterolhomeostasis
  • Freeradicals
  • Neurodegenerativedisease


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