Cholesterol metabolites exported from human brain

Iuliano, Luigi; Crick, Peter J.; Zerbinati, Chiara; Tritapepe, Luigi; Abdel-Khalik, Jonas; Poirot, Marc; Wang, Yuqin; Griffiths, William J.

doi:10.1016/j.steroids.2015.01.026

Cited by 76 publications

(63 citation statements)

References 28 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Heverin et al (42) have shown that 26-HC is imported to the brain, whereas Meaney et al (43) have shown that its acidic metabolite 7αH,3O-CA is exported from the brain to circulation. Further studies by Iuliano et al (44) have shown that a precursor of this acid, 7α,26-dihydroxycholest-4-en-3-one (7α,26-diHCO), is also exported from the brain to circulation, as is its isomer 7α,25-diHCO. In another study, Ogundare et al (45) have shown that multiple parts of the acidic pathway of bile acid biosynthesis are active in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Defective cholesterol metabolism in amyotrophic lateral sclerosis

Abdel-Khalik

Yutuc

Crick

et al. 2017

Journal of Lipid Research

Self Cite

127

158

View full text Add to dashboard Cite

As neurons die, cholesterol is released in the central nervous system (CNS); hence, this sterol and its metabolites may represent a biomarker of neurodegeneration, including in amyotrophic lateral sclerosis (ALS), in which altered cholesterol levels have been linked to prognosis. More than 40 different sterols were quantified in serum and cerebrospinal fluid (CSF) from ALS patients and healthy controls. In CSF, the concentration of cholesterol was found to be elevated in ALS samples. When CSF metabolite levels were normalized to cholesterol, the cholesterol metabolite 3β,7α-dihydroxycholest-5-en-26-oic acid, along with its precursor 3β-hydroxycholest-5-en-26-oic acid and product 7α-hydroxy-3-oxocholest-4-en-26-oic acid, were reduced in concentration, whereas metabolites known to be imported from the circulation into the CNS were not found to differ in concentration between groups. Analysis of serum revealed that (25R)26-hydroxycholesterol, the immediate precursor of 3β-hydroxycholest-5-en-26-oic acid, was reduced in concentration in ALS patients compared with controls. We conclude that the acidic branch of bile acid biosynthesis, known to be operative in-part in the brain, is defective in ALS, leading to a failure of the CNS to remove excess cholesterol, which may be toxic to neuronal cells, compounded by a reduction in neuroprotective 3β,7α-dihydroxycholest-5-en-26-oic acid.

show abstract

Section: Discussionmentioning

confidence: 99%

Defective cholesterol metabolism in amyotrophic lateral sclerosis

Abdel-Khalik

Yutuc

Crick

et al. 2017

Journal of Lipid Research

Self Cite

127

158

View full text Add to dashboard Cite

show abstract

“…OS were determined by high performance gas chromatography coupled to mass spectometry (GC-MS) detection using deuterium-labelled internal standards, as described previously Iuliano et al [25]. Briefly, 10 µl butylated hydroxytoluene (BHT) in ethanol (5 mg/ml) and 50 µl EDTA (10 mg/ml) were added to a solution of 1 ml plasma and [26]. A list of the OS measured is provided in…”

Section: 3measure Of Os Concentrationsmentioning

confidence: 99%

Circulating oxysterol metabolites as potential new surrogate markers in patients with hormone receptor-positive breast cancer: Results of the OXYTAM study

Dalenc

Iuliano

Filleron

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

Self Cite

View full text Add to dashboard Cite

“…respectively, at position C-24 [1,2]. Supplementation of foods with 60 plant sterols and daily intake of 2 g plant sterol esters leads to a 61 nearly 10% lowering of cholesterol in the blood and a slight 62 increase of the serum levels of these plant sterols [1,3] [10]. The same group recently reported on flux of unesteri-83 fied 7a-25-and 7a-(25R)26-dihydroxycholesterol from the brain 84 into the periphery [11] from the same material.…”

mentioning

confidence: 99%