FIGURE 2.

Differential protein and metabolite enrichment in PM females. (A) Proteomics analysis was carried out in PBMC from PM females 29–63 year old and age-matched controls. Proteins detected in both PM and non-carriers were uploaded with their corresponding fold change values (see Supplementary Dataset) to STRING. Interactomes were algorithmically generated based on direct associations (physical or functional) between eligible proteins. The interactomes are color coded with blue nodes representing proteins that were down-regulated, red upregulated in PM, and clear when there were detected but whose levels were not statistically different between diagnostic groups. The shading of each node is correlated with the magnitude of the fold change. Differentially regulated metabolic pathways included carbon metabolism, metabolism of RNA, proteins, amino acids, and cellular response to oxidative stress. (B) A subset of differentially regulated proteins (Supplementary Dataset, tabs highlighted in gray) had key roles in mitochondrial function, glycolysis, fatty acid and amino acid metabolism, as well as in RNA processing (pathways reported in Supplementary Figures 1–3) and pathways affected in neurodegeneration. (C) Metabolomics analysis was performed in plasma from 8 controls and 7 age-matched PM carriers, 24–52 year, and age-matched controls. Differentially enriched metabolites are shown, with their respective p values, in Supplementary Figure 4. A forest plot was built with the odds ratios (X axis) and the 95% CI (error bars) calculated with control values for each selected metabolite based on its role in glycolysis and mitochondrial metabolism. In red are metabolites with statistically significant OR, indicating a higher probability to be affected in the PM, and as such considered as putative biomarkers for female carriers.