title: 24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival.
abstract: The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors: Min-Yu
authors: MY
authors: Sun
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors: Andrew J
authors: AJ
authors: Linsenbardt
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors: Christine M
authors: CM
authors: Emnett
authors: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Lawrence N
authors: LN
authors: Eisenman
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Yukitoshi
authors: Y
authors: Izumi
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA.
authors: Charles F
authors: CF
authors: Zorumski
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA menneris@wustl.edu.
authors: Steve
authors: S
authors: Mennerick
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000072556:Cholesterol 24-Hydroxylase / Q000235:genetics; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D006888:Hydroxycholesterols; D016194:Receptors, N-Methyl-D-Aspartate; D000072556:Cholesterol 24-Hydroxylase
keywords: Alzheimer’s disease; NMDA; apoptosis; cholesterol. 24(S)-hydroxycholesterol; glutamate
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