Table 3.
Central nodes of the DEG network are associated with PD (Fig. 6c).
| Node gene | Role in Parkinson’s disease |
|---|---|
| HSPA8 (also known as HSP73, HSC70) | Disaggregation of α-synuclein amyloid fibrils85 |
| Autophagy, part of the catabolic pathway for α-synuclein86 | |
| Mediates mitophagy by regulating the stability of PINK1 protein87 | |
| Impaired gene expression in sporadic PD88 | |
| EEF1A1 | Mediates activation of heat-shock transcription factor HSF1, prevents α-synuclein aggregation90 |
| Interacts with Parkin (PARK2)82 | |
| HNRNPC | Interacts with Parkin (PARK2)82 |
| Part of the poly ADP-ribose (PAR) cell death pathway accountable for selective dopaminergic neuronal loss99 | |
| PSMA4 | Part of the Parkinson’s disease KEGG pathway92,93 |
| Interacts with Parkin (PARK2) and FBX07 (PARK15)82 | |
| CYCS | Role in aggregation of alpha-synuclein170 |
| CTD gene-disease associations - Parkinson disease gene set63 | |
| ACTN1 | Interacts with DJ-1 (PARK7)82 |
| It is a binding partner of mitochondrial-shaping proteins171 | |
| PGK1 | PGK1 mutation causes vulnerability to parkinsonism172 |
| Activation of PGK1 partially restored motor function and slowed disease progression69 | |
| PHB | Regulates dopaminergic cell death in substantia nigra173 |
| SHH | Play a role in neuroinflammatory response in the MPTP model of Parkinson’s disease174 |
| BRCA2 | Deubiquitinase plays a role in neuronal inflammation175 |
| VPS39 | It is part of the endocytic membrane trafficking pathway involved in PD and its methylation rates are associated with Parkinson’s disease risk176 |
| Plays complex functions in endocytic and autophagic pathways177 | |
| UQCRFS1 | KEGG pathway, Parkinson disease92,93 |
| CNTNAP2 | Differentially expressed in the presence of LRRK2 G2019S mutation, associated with PD97 |
| GWASdb SNP-disease associations, Parkinson’s disease gene set63 | |
| Plays a role in the formation of protein aggregates and PD95,96 | |
| CUL3 | Ubiquitin ligase, a potential drug target for Parkinson’s disease84 |
| PLCB4 | GWAS - Parkinson’s disease63 |
| Motor defect consistent with ataxia in Plcb4-null mice100 | |
| EGLN3 | GEO signatures of differentially expressed genes for diseases—Parkinson’s Disease_Substantia Nigra63 |
| Prolyl hydroxylase targets substrates for ubiquitination178 | |
| RALGPS2 | Targets include Nurr1, which is associated with Parkinson disease63 |
Central nodes were determined using the Gephi visualization platform. They represent points of convergence of the network (Supplementary Fig. 5). Since these nodes have already been linked to PD pathways, many more DEGs might also contribute to PD pathology through these pathways. These nodes not only provide a point of convergence for DEGs identified in our study, but they also interact with several PARK genes, suggesting that PARK proteins may also converge on the pathways identified here (Supplementary Fig. 7).