title: 25-Hydroxycholesterol is involved in the pathogenesis of amyotrophic lateral sclerosis.
abstract: This study aimed to evaluate the levels of three major hydroxycholesterols (24-, 25-, and 27-hydroxycholesterols) in the serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), as well as to show their role in the pathogenesis of ALS experimental models. The level of 25-hydroxycholesterol were higher in untreated ALS patients (n = 30) than in controls without ALS (n = 33) and ALS patients treated with riluzole (n = 9) both in their serum and CSF. The level of 25-hydroxycholesterol in the serum of ALS patients were significantly associated with their disease severity and rate of progression. In the motor neuron-like cell line (NSC34) with the human mutant G93A superoxide dismutase 1 gene (mSOD1-G93A), 25-hydroxycholesterol induced motor neuronal death/ apoptosis via glycogen synthase kinase-3β and liver X receptor pathways; riluzole treatment attenuated these effects. The expressions of enzymes that synthesize 25-hydroxycholesterol were significantly increased in the brains of early symptomatic mSOD1G93A mice. Our data, obtained from patients with ALS, a cellular model of ALS, and an animal model of ALS, suggests that 25-hydroxycholesterol could be actively involved in the pathogenesis of ALS, mostly in the early symptomatic disease stage, by mediating neuronal apoptosis.
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hanyang University, College of Medicine, Seoul, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Noh
authors.affiliation: Department of Neurology, Seoul National University Bundang hospital, Seong Nam, Korea.
authors.forename: Heejaung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Cheon
authors.affiliation: Doping Control Center, Korea Institute of Science and Technology, Korea.
authors.forename: Kang Mi
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Doping Control Center, Korea Institute of Science and Technology, Korea.
authors.forename: Jaeick
authors.initials: J
authors.lastname: Lee
authors.affiliation: Doping Control Center, Korea Institute of Science and Technology, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Cha
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.|Department of Neurology, Seoul National University Bundang hospital, Seong Nam, Korea.
authors.forename: Kyung Seok
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Department of Neurology, Hanyang University, College of Medicine, Seoul, Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged
chemical_list: D006888:Hydroxycholesterols; C007997:25-hydroxycholesterol
keywords: 25-hydroxycholesterol; amyotrophic lateral sclerosis; cholesterol; hydroxycholesterol; liver X receptor