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Sex stratification of gene expression changes in Parkinson’s Disease
Parkinson’s disease (PD) is the second-leading cause of death among neurodegenerative disorders after Alzheimer’s disease (AD), affecting around 2% of the population. It is expected that the incidence of PD will exceed 12 million by 2040. Meanwhile, there is a recognized difference in the molecular...
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AUC Knowledge Fountain
2027
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| Summary: | Parkinson’s disease (PD) is the second-leading cause of death among neurodegenerative disorders after Alzheimer’s disease (AD), affecting around 2% of the population. It is expected that the incidence of PD will exceed 12 million by 2040. Meanwhile, there is a recognized difference in the molecular and phenotypical expression of the disease as well as in the response to treatment between men and women. Men have twice the incidence of PD compared to women, who have a late onset and worse prognosis that is usually associated with menopause. To delineate these disparities, transcriptomic data obtained from 1,392 peripheral blood samples, leveraging the PPMI database (Parkinson’s Progression Marker’s Initiative), were used to perform a sex stratified differential gene expression analysis. Sex specific differentially expressed genes were identified, which revealed sex divergent alterations in peripheral inflammatory response and female-specific alterations in chromatin remodeling pathways. Based on sex specific pathway enrichment analysis and protein-protein interaction (PPI) analysis, a subset of the female-specific differentially expressed genes was found to be transcriptional targets of estrogen through ER-α, suggesting the pivotal role of estrogen in mediating sex-dependent alterations in PD. These results may open new avenues towards a sex informed diagnosis and treatment of PD. |
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