Article (Scientific journals)
Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach
Giovagnoni, Caterina; Ali, Muhammad; Eijssen, Lars M. T. et al.
2021In Neurobiology of Aging, in press (in press)
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Keywords :
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 center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group)
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Life sciences: Multidisciplinary, general & others
Human health sciences: Multidisciplinary, general & others
Neurology
Biotechnology
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.
More authors (6 more) Less
External co-authors :
yes
Language :
English
Title :
Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach
Publication date :
2021
Journal title :
Neurobiology of Aging
ISSN :
1558-1497
Publisher :
Elsevier, New York, Netherlands
Volume :
in press
Issue :
in press
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR10243098 - Targeting Epigenetic Dysregulation In The Brainstem In Alzheimer'S Disease, 2015 (01/08/2016-31/07/2019) - Antonio Del Sol Mesa
Name of the research project :
EPIGE(NE5HT)ICS-AD
Funders :
FNR - Fonds National de la Recherche [LU]
Fondation Wivine Luxembourg
Available on ORBilu :
since 03 February 2021

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