Reference : Gender-specific expression of ubiquitin-specific peptidase 9 modulates tau expression...
Scientific journals : Article
Life sciences : Biotechnology
Life sciences : Multidisciplinary, general & others
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/28838
Gender-specific expression of ubiquitin-specific peptidase 9 modulates tau expression and phosphorylation: possible implications for tauopathies
English
Köglsberger, Sandra [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Cordero Maldonado, Maria Lorena [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Antony, Paul [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Forster, Julia [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Garcia, Pierre [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Buttini, Manuel [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Crawford, Alexander Dettmar [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Dec-2017
Molecular Neurobiology
54
10
7979–7993
Yes (verified by ORBilu)
International
0893-7648
1559-1182
[en] Alzheimer's disease ; gender differences ; ubiquitin ; tau ; neurodegeneration ; USP9 ; microarray ; zebrafish ; DU145 ; gene expression ; alpha-synuclein ; GSK3B ; MARK4 ; transcriptomics ; tauopathies
[en] Public transcriptomics studies have shown that several genes display pronounced gender differences in their expression in the human brain, which may influence the manifestations and risk for neuronal disorders. Here we apply a transcriptome-wide analysis to discover genes with gender-specific expression and significant alterations in public post mortem brain tissue from Alzheimer’s disease (AD) patients compared to controls. We identify the sex-linked ubiquitin specific peptidase 9 (USP9) as an outstanding candidate gene with highly significant expression differences between the genders and male-specific under-expression in AD. Since previous studies have shown that USP9 can modulate the phosphorylation of the AD-associated protein MAPT, we investigate functional associations between USP9 and MAPT in further detail. After observing a high positive correlation between the expression of USP9 and MAPT in the public transcriptomics data, we show that USP9 knockdown results in significantly decreased MAPT expression in a DU145 cell culture model and a concentration-dependent decrease for the MAPT orthologs mapta and maptb in a zebrafish model. From the analysis of microarray and qRT-PCR experiments for the knockdown in DU145 cells and prior knowledge from the literature, we derive a data-congruent model for a USP9-dependent regulatory mechanism modulating MAPT expression via BACH1 and SMAD4. Overall, the analyses suggest USP9 may contribute to molecular gender differences observed in tauopathies and provide a new target for intervention strategies to modulate MAPT expression.
Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Fondation Wivine Luxembourg ; Geoffrey Been Alzheimer’s Initiative and BrightFocus Foundation
Researchers ; Professionals ; Students ; General public
http://hdl.handle.net/10993/28838
10.1007/s12035-016-0299-z
The original publication is available at http://link.springer.com/article/10.1007/s12035-016-0299-z

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