| Reference : Systems level analysis of sex-dependent gene expression changes in Parkinson’s disease |
| Scientific journals : Article | |||
| Life sciences : Multidisciplinary, general & others | |||
| Systems Biomedicine | |||
| http://hdl.handle.net/10993/53268 | |||
| Systems level analysis of sex-dependent gene expression changes in Parkinson’s disease | |
| English | |
Tranchevent, Leon-Charles  [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science >] | |
| Halder, Rashi [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services >] | |
| Glaab, Enrico [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science >] | |
| 2023 | |
| NPJ Parkinson's Disease | |
| Nature Publishing Group | |
| 9 | |
| 8 | |
| Yes | |
| 2373-8057 | |
| New-York | |
| United States - New York | |
| [en] Parkinson’s disease ; meta-analysis ; sex differences ; sexual dimorphism | |
| [en] Parkinson’s disease (PD) is a heterogeneous disorder, and among the factors which influence the symptom profile, biological sex has been reported to play a significant role. While males have a higher age-adjusted disease incidence and are more frequently affected by muscle rigidity, females present more often with disabling tremors. The molecular mechanisms involved in these differences are still largely unknown, and an improved understanding of the relevant factors may open new avenues for pharmacological disease modification.
To help address this challenge, we conducted a meta-analysis of disease-associated molecular sex differences in brain transcriptomics data from case/control studies. Both sex-specific (alteration in only one sex) and sex-dimorphic changes (changes in both sexes, but with opposite direction) were identified. Using further systems level pathway and network analyses, coordinated sex-related alterations were studied. These analyses revealed significant disease-associated sex differences in mitochondrial pathways and highlight specific regulatory factors whose activity changes can explain downstream network alterations, propagated through gene regulatory cascades. Single-cell expression data analyses confirmed the main pathway-level changes observed in bulk transcriptomics data. Overall, our analyses revealed significant sex disparities in PD-associated transcriptomic changes, resulting in coordinated modulations of molecular processes. Among the regulatory factors involved, NR4A2 has already been reported to harbour rare mutations in familial PD and its pharmacological activation confers neuroprotective effects in toxin-induced models of Parkinsonism. Our observations suggest that NR4A2 may warrant further research as a potential adjuvant therapeutic target to address a subset of pathological molecular features of PD that display sex-associated profiles. | |
| Researchers ; Professionals ; Students ; General public ; Others | |
| http://hdl.handle.net/10993/53268 | |
| FnR ; FNR11651464 > Enrico Glaab > PD-Strat > Multi-dimensional Stratification Of Parkinson’S Disease Patients For Personalised Interventions > 01/07/2018 > 30/06/2021 > 2017; ERA-Net ERACoSysMed JTC-2 project PD-Strat (INTER/11651464) |
| File(s) associated to this reference | ||||||||||||||
|
Fulltext file(s):
| ||||||||||||||
All documents in ORBilu are protected by a user license.
