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Tytuł pozycji:

Cholesteryl ester levels are elevated in the caudate and putamen of Huntington's disease patients.

Tytuł:
Cholesteryl ester levels are elevated in the caudate and putamen of Huntington's disease patients.
Autorzy:
Phillips GR; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.; School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia.; Molecular Horizons, University of Wollongong, Wollongong, NSW, 2522, Australia.
Hancock SE; School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
Brown SHJ; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.; Molecular Horizons, University of Wollongong, Wollongong, NSW, 2522, Australia.; School of Chemistry and Molecular Biosciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
Jenner AM; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, 2052, Australia.
Kreilaus F; School of Medicine, Western Sydney University, Sydney, NSW, 2560, Australia.
Newell KA; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.; School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia.; Molecular Horizons, University of Wollongong, Wollongong, NSW, 2522, Australia.
Mitchell TW; Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia. .; School of Medicine, University of Wollongong, Wollongong, NSW, 2522, Australia. .; Molecular Horizons, University of Wollongong, Wollongong, NSW, 2522, Australia. .
Źródło:
Scientific reports [Sci Rep] 2020 Nov 20; Vol. 10 (1), pp. 20314. Date of Electronic Publication: 2020 Nov 20.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Caudate Nucleus/*chemistry
Cholesterol Esters/*analysis
Huntington Disease/*pathology
Putamen/*chemistry
Acetyl-CoA C-Acetyltransferase/analysis ; Acetyl-CoA C-Acetyltransferase/metabolism ; Aged ; Aged, 80 and over ; Animals ; Case-Control Studies ; Caudate Nucleus/pathology ; Cerebellum/metabolism ; Cerebellum/pathology ; Cholesterol Esters/metabolism ; Female ; Humans ; Male ; Mass Spectrometry ; Mice ; Middle Aged ; Putamen/pathology
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Substance Nomenclature:
0 (Cholesterol Esters)
EC 2.3.1.9 (ACAT1 protein, human)
EC 2.3.1.9 (Acetyl-CoA C-Acetyltransferase)
Entry Date(s):
Date Created: 20201121 Date Completed: 20210330 Latest Revision: 20210330
Update Code:
20240105
PubMed Central ID:
PMC7680097
DOI:
10.1038/s41598-020-76973-8
PMID:
33219259
Czasopismo naukowe
Huntington's disease (HD) is an autosomal dominant neurodegenerative illness caused by a mutation in the huntingtin gene (HTT) and subsequent protein (mhtt), to which the brain shows a region-specific vulnerability. Disturbances in neural cholesterol metabolism are established in HD human, murine and cell studies; however, cholesteryl esters (CE), which store and transport cholesterol in the brain, have not been investigated in human studies. This study aimed to identify region-specific alterations in the concentrations of CE in HD. The Victorian Brain Bank provided post-mortem tissue from 13 HD subjects and 13 age and sex-matched controls. Lipids were extracted from the caudate, putamen and cerebellum, and CE were quantified using targeted mass spectrometry. ACAT 1 protein expression was measured by western blot. CE concentrations were elevated in HD caudate and putamen compared to controls, with the elevation more pronounced in the caudate. No differences in the expression of ACAT1 were identified in the striatum. No remarkable differences in CE were detected in HD cerebellum. The striatal region-specific differences in CE profiles indicate functional subareas of lipid disturbance in HD. The increased CE concentration may have been induced as a compensatory mechanism to reduce cholesterol accumulation.
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