Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson' Disease

Disrupted iron metabolism has been implicated in the pathogenesis of Parkinson's disease (PD), a progressive neurodegenerative disorder that severely affects movement and coordination, yet the molecular mechanisms underlying this association remain unknown. To this end, we performed a transcriptomic meta-analysis of four blood microarrays in PD. We observed a significant downregulation of genes related to hemoglobin including, hemoglobin delta (HBD), alpha hemoglobin stabilizing protein (ASHP), genes implicated in iron metabolism including, solute carrier family 11 member 2 (SLC11A2), ferrochelatase (FECH), and erythrocyte-specific genes including erythrocyte membrane protein (EPB42), and 5 0 -aminolevulinate synthase 2 (ALAS2). Pathway and network analysis identified enrichment in processes related to mitochondrial membrane, oxygen transport, oxygen and heme binding, hemoglobin complex, erythrocyte development, tetrapyrrole metabolism and the spliceosome. Collectively, we identified a subnetwork of genes in blood that may provide a molecular explanation for the disrupted hemoglobin and iron metabolism in the pathogenesis of PD.