Reference : Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biotechnology Life sciences : Multidisciplinary, general & others Human health sciences : Neurology Human health sciences : Multidisciplinary, general & others
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/46078

Title :	Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach
Language :	English
Author, co-author :	Giovagnoni, Caterina [> >]
	Ali, Muhammad [> >]
	Eijssen, Lars M. T. [> >]
	Maes, Richard [> >]
	Choe, Kyonghwan [> >]
	Mulder, Monique [> >]
	Kleinjans, Jos [> >]
	del Sol, Antonio []
	Glaab, Enrico [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science]
	Mastroeni, Diego [> >]
	Delvaux, Elaine [> >]
	Coleman, Paul [> >]
	Losen, Mario [> >]
	Pishva, Ehsan [> >]
	Martinez, Pilar Martinez [> >]
	van den Hove, Daniel L. A. [> >]
Publication date :	2021
Journal title :	Neurobiology of Aging
Publisher :	Elsevier
Volume :	in press
Issue/season :	in press
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	0197-4580
e-ISSN :	1558-1497
City :	New York
Country :	Netherlands
Keywords :	[en] Alzheimer's disease ; aging ; sphingolipids ; regulatory networks ; pathways ; bioinformatics ; epigenetics ; disease network analysis
Abstract :	[en] Sphingolipids (SLs) are bioactive lipids involved in various important physiological functions. The SL pathway has been shown to be affected in several brain-related disorders, including Alzheimer’s disease (AD). Recent evidence suggests that epigenetic dysregulation plays an important role in the pathogenesis of AD as well. Here, we use an integrative approach to better understand the relationship between epigenetic and transcriptomic processes in regulating SL function in the middle temporal gyrus of AD patients. Transcriptomic analysis of 252 SL-related genes, selected based on GO term annotations, from 46 AD patients and 32 healthy age-matched controls, revealed 103 differentially expressed SL-related genes in AD patients. Additionally, methylomic analysis of the same subjects revealed parallel hydroxymethylation changes in PTGIS, GBA, and ITGB2 in AD. Subsequent gene regulatory network-based analysis identified three candidate genes, i.e. SELPLG, SPHK1 and CAV1 whose alteration holds the potential to revert the gene expression program from a diseased towards a healthy state. Together, this epigenomic and transcriptomic approach highlights the importance of SL-related genes in AD, and may provide novel biomarkers and therapeutic alternatives to traditionally investigated biological pathways in AD.
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Funders :	Fonds National de la Recherche - FnR ; Fondation Wivine Luxembourg
Name of the research project :	EPIGE(NE5HT)ICS-AD
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/10993/46078
Mentions required by the publisher for OA :	The link to the original publication will be provided once available.
FnR project :	FnR ; FNR10243098 > Antonio Del Sol Mesa > EPIGE(NE5HT)ICS-AD > Targeting Epigenetic Dysregulation In The Brainstem In Alzheimer’S Disease > 01/08/2016 > 31/07/2019 > 2015

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