title: New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death.
abstract: 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.
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan. Electronic address: nnoguchi@mail.doshisha.ac.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Urano
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Takabe
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000235:genetics; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D000071518:Liver X Receptors; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors
keywords: 24(S)-Hydroxycholesterol; CYP46A1; Cell death; Cholesterol homeostasis; Free radicals; Neurodegenerative disease