Abstract
BackgroundParkinson’s Disease (PD) and Hutchinson-Gilford Progeria Syndrome (HGPS) are two heterogeneous disorders, which both display molecular and clinical alterations associated with the aging process. However, similarities and differences between molecular changes in these two disorders have not yet been investigated systematically at the level of individual biomolecules and shared molecular network alterations.MethodsHere, we perform a comparative meta-analysis and network analysis of human transcriptomics data from case-control studies for both diseases to investigate common susceptibility genes and sub-networks in PD and HGPS. Alzheimer’s disease (AD) and primary melanoma (PM) were included as controls to confirm that the identified overlapping susceptibility genes for PD and HGPS are non-generic.ResultsWe find statistically significant, overlapping genes and cellular processes with significant alterations in both diseases. Interestingly, the majority of these shared affected genes display changes with opposite directionality, indicating that shared susceptible cellular processes undergo different mechanistic changes in PD and HGPS. A complementary regulatory network analysis also reveals that the altered genes in PD and HGPS both contain targets controlled by the upstream regulator CDC5L.ConclusionsOverall, our analyses reveal a significant overlap of affected cellular processes and molecular sub-networks in PD and HGPS, including changes in aging-related processes that may reflect key susceptibility factors associated with age-related risk for PD.
Highlights
Parkinson’s Disease (PD) and Hutchinson-Gilford Progeria Syndrome (HGPS) are two heterogeneous disorders, which both display molecular and clinical alterations associated with the aging process
We identified 13 differentially expressed genes (DEGs), 66 Gene Ontology (GO) biological processes, 12 GO terms associated with molecular subnetworks and one transcription factor (TF) with shared significance in PD and HGPS, and no significant alteration for the two control diseases
DEGs changing in the same direction in PD and HGPS : these genes may serve for further investigation as candidate surrogate biomarkers for PD risk stratification and/or early diagnosis of PD;
Summary
Parkinson’s Disease (PD) and Hutchinson-Gilford Progeria Syndrome (HGPS) are two heterogeneous disorders, which both display molecular and clinical alterations associated with the aging process. Previous studies have shown that many of the features associated with HGPS reflect a premature onset of pathologies commonly associated with adult aging and age-related neurodegenerative diseases [12, 13]. These observations suggest that a more systematic investigation of shared molecular alterations or shared susceptibility factors in PD and HGPS could provide new insights on a subset of generic, aging-associated pathological changes in PD that may already influence the early, pre-motor stages of the disease
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