Whole body cholesterol metabolism is impaired in Huntington's disease

被引：71

作者：

Leoni, V. ^{[1
]}

Mariotti, C. ^{[2
]}

Nanetti, L. ^{[2
]}

Salvatore, E. ^{[3
]}

Squitieri, F. ^{[4
]}

Bentivoglio, A. R. ^{[5
]}

del Poggio, M. Bandettini ^{[6
]}

Piacentini, S. ^{[7
]}

Monza, D. ^{[2
]}

Valenza, M. ^{[8
,9
]}

Cattaneo, E. ^{[8
,9
]}

Di Donato, S. ^{[2
]}

机构：

[1] Fdn IRCCS Ist Neurol Carlo Besta, Lab Clin Pathol & Med Genet, I-20133 Milan, MI, Italy

[2] Fdn IRCCS Ist Neurol Carlo Besta, Unit Genet Neurodegenerat & Metab Dis, I-20133 Milan, MI, Italy

[3] Univ Naples Federico II, Dept Neurol, Naples, Italy

[4] IRCCS Neuromed, Neuropharmacol Unit, Pozzilli, Italy

[5] Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy

[6] Univ Genoa, Dept Neurosci Ophtalmol & Genet, Genoa, Italy

[7] Univ Florence, Dept Neurol, Florence, Italy

[8] Univ Milan, Dept Pharmacol Sci, I-20122 Milan, Italy

[9] Univ Milan, Ctr Stem Cell Res, I-20122 Milan, Italy

来源：

NEUROSCIENCE LETTERS | 2011年 / 494卷 / 03期

关键词：

Oxysterol; Cholesterol; Neurodegeneration; Atrophy; Metabolism; BIOSYNTHESIS PATHWAY; BRAIN; PLASMA; 24S-HYDROXYCHOLESTEROL; DYSFUNCTION; MANIFEST; VOLUMES; MRI;

D O I：

10.1016/j.neulet.2011.03.025

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We previously reported impaired cholesterol biosynthesis in rodent Huntington Disease (HD) models and HD patients' fibroblasts and post mortem brains. We also found that plasma levels of 24S-hydroxycholesterol (24OHC), the brain specific elimination product of cholesterol considered a marker of brain cholesterol turnover, were significantly reduced in HD patients at any disease stage. In the present study we analysed by mass spectrometry the fasting plasma levels of cholesterol, its biosynthetic precursors lanosterol and lathosterol, of the whole-body elimination products 27-hydroxycholesterol and of brain 24OHC in a cohort of premanifest and HD patients at different disease stages. We found that the cholesterol precursors lanosterol and lathosterol (both index of whole body cholesterol synthesis), the levels of the bile acid precursor 27-hydroxycholesterol, and of the brain specific 24OHC, were all significantly reduced in manifest HD patients, suggesting that whole-body and brain cholesterol homeostasis are both impaired in HD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：245 / 249

页数：5

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