Gordillo-Gonzalez, F. | bioRxiv Science

bioRxiv2026

Transposable elements as new players to decipher sex differences in Parkinson Disease

We present a novel integrative analysis of transposable elements (TEs) in 4 single cell RNA-seq (scRNA-seq) datasets of postmortem substantia nigra pars compacta samples of Parkinson Disease (PD) patients matched healthy controls, with the objective of building a cell-type specific trustworthy atlas of TEs that may clarify the role of TEs in sex differences in PD. We have used the soloTE tool to evaluate the TEs expression changes across all snRNA-seq studies identified in our previous systematic review, and then integrated the results using meta-analysis techniques. Finally, we evaluated the possible associations between TEs and protein coding genes by integrating our previous results in this matter with the information of TEs obtained, in order to propose the possible action mechanism by which some of the TEs contribute to PD.

bioinformatics↗

bioRxiv2024

Uncovering sex differences in Parkinson's Disease through metaanalysis of single cell transcriptomic studies

Abundant evidence supports the significant impact of biological sex on various aspects of Parkinson Disease (PD), including incidence, progression, symptoms or response to treatment. The incidence and prevalence of the disease is higher in males, while its age of onset is earlier than in females. There are also sex differences in the symptomatology, both motor and non-motor. In female PD, tremor, pain, depression and dysphagia are predominant, whereas in male PD, freezing of gait, camptocormia, cognitive impairment and urinary dysfunction are more common. Likewise, there are sex differences in the pathophysiology of the disease, related to most of the pathological processes of PD, as is the case of the greater activation of microglia in males or the lower oxidative stress in females. All these findings support the idea that different molecular mechanisms may be involved in PD depending on the sex of the patient. Some explanations for these events are related to biological, genetic, hormonal or environmental factors, such as the possible anti-inflammatory and neuroprotective effect of estrogens. However, the underlying molecular mechanisms have not yet been fully described. Our results show sex differences in gene expression, cell-cell communication and pathway activation in all major brain cell types, highlighting the presence of greater neuroinflammation in men and greater neurodegeneration in the SNpc in men, with the latter appearing to be inverted between sexes when observed in the cortical zone. Finally, we have made all the results available in a publicly accessible webtool, in order to allow the exploration of results to other researchers and to broaden the molecular-level understanding of PD sex differences.

neuroscience↗