Reference : Modelling gender-specific regulation of tau in Alzheimer’s disease
Scientific Presentations in Universities or Research Centers : Scientific presentation in universities or research centers
Life sciences : Biotechnology
Human health sciences : Neurology
Human health sciences : Multidisciplinary, general & others
Systems Biomedicine; Computational Sciences
Modelling gender-specific regulation of tau in Alzheimer’s disease
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Luxembourg Centre for Systems Biomedicine Annual Donor Thank You Event 2016
[en] Alzheimer's disease ; tau ; tauopathy ; zebrafish ; cell culture ; DU145 ; microarray ; gene expression ; neurodegeneration ; gender differences
[en] Public transcriptomic 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 postmortem 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 underexpression 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 ; BrightFocus Foundation
R-AGR-0609 > Donation - Biomedicine Alzheimer > 01/06/2015 - 31/05/2016 > SCHNEIDER Reinhard
Researchers ; Professionals ; Students ; General public

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