The Cerebrospinal Fluid Profile of Cholesterol Metabolites in Parkinson's Disease and Their Association With Disease State and Clinical Features.

bile acid biosynthesis dihydroxycholesterol mass spectrometry oxysterol sterol

Journal

Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824

Informations de publication

Date de publication:
2021
Historique:
received: 25 03 2021
accepted: 28 05 2021
entrez: 16 9 2021
pubmed: 17 9 2021
medline: 17 9 2021
Statut: epublish

Résumé

Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson's disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a second oxysterol 7α,x,y-trihydroxycholest-4-en-3-one (7α,x,y-triHCO), whose exact structure is unknown, were found to be significantly elevated in PD CSF. The likely location of the additional hydroxy groups on the second oxysterol are on the sterol side-chain. We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression.

Identifiants

pubmed: 34526889
doi: 10.3389/fnagi.2021.685594
pmc: PMC8435905
doi:

Types de publication

Journal Article

Langues

eng

Pagination

685594

Subventions

Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R007446/1
Pays : United Kingdom

Informations de copyright

Copyright © 2021 Griffiths, Abdel-Khalik, Moore, Wijeyekoon, Crick, Yutuc, Farrell, Breen, Williams-Gray, Theofilopoulos, Arenas, Trupp, Barker and Wang.

Déclaration de conflit d'intérêts

WG, PC, and YW were listed as inventors on the Swansea University patent “Kit and method for quantitative detection of steroids,” US9851368B2, licensed to Avanti Polar Lipids Inc., and Cayman Chemical Company by Swansea University. WG, JA-K, PC, EY, ST, EA, and YW were shareholders in CholesteniX Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Annu Rev Biochem. 2003;72:137-74
pubmed: 12543708
Steroids. 2012 May;77(6):575-7
pubmed: 22366074
Prostaglandins Other Lipid Mediat. 2020 Apr;147:106381
pubmed: 31698146
Front Neurol. 2018 Sep 07;9:756
pubmed: 30245667
J Lipid Res. 2004 Aug;45(8):1375-97
pubmed: 15254070
Chem Phys Lipids. 2011 Sep;164(6):515-24
pubmed: 21515244
Metabolites. 2021 Jan 04;11(1):
pubmed: 33406628
Biochem J. 2014 Jul 1;461(1):125-35
pubmed: 24735479
J Lipid Res. 2009 Nov;50(11):2139-47
pubmed: 19357427
Int J Mol Sci. 2019 Sep 12;20(18):
pubmed: 31547302
Neurosci Lett. 2013 Oct 25;555:102-5
pubmed: 24035896
Free Radic Biol Med. 2019 Apr;134:42-52
pubmed: 30578919
Cell Rep Med. 2020 Nov 17;1(8):100138
pubmed: 33294859
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
J Lipid Res. 2007 Apr;48(4):944-51
pubmed: 17251592
Clin Chem Lab Med. 2004 Feb;42(2):186-91
pubmed: 15061359
Nat Rev Immunol. 2016 Jan;16(1):22-34
pubmed: 26711676
Brain Behav Immun. 2013 Oct;33:183-9
pubmed: 23911592
Biochem Pharmacol. 2013 Jul 1;86(1):3-14
pubmed: 23395696
Biochimie. 2018 Oct;153:86-98
pubmed: 29960034
J Lipid Res. 2017 Jan;58(1):267-278
pubmed: 27811233
Mol Neurobiol. 2017 Dec;54(10):8009-8020
pubmed: 27878760
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9799-804
pubmed: 8790411
Clin Chem. 2015 Feb;61(2):400-11
pubmed: 25512642
J Biol Chem. 2010 Feb 12;285(7):4666-79
pubmed: 19996111
J Lipid Res. 2005 May;46(5):1047-52
pubmed: 15741649

Auteurs

William J Griffiths (WJ)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Jonas Abdel-Khalik (J)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Sarah F Moore (SF)

Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.

Ruwani S Wijeyekoon (RS)

Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.

Peter J Crick (PJ)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Eylan Yutuc (E)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Krista Farrell (K)

Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.

David P Breen (DP)

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom.
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.

Caroline H Williams-Gray (CH)

Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.

Spyridon Theofilopoulos (S)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Ernest Arenas (E)

Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Miles Trupp (M)

Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.

Roger A Barker (RA)

Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.

Yuqin Wang (Y)

Swansea University Medical School, ILS1 Building, Swansea, United Kingdom.

Classifications MeSH