Table 4.
Main hubs in SN-CT and SN-PD networks*.
| Gene | Gene-gene links | Gene product and/or biological function | |
|---|---|---|---|
| CT | PD | ||
| SIRT1 | 19 | 10 | Nicotinamide adenine dinucleotide- (NAD+-) dependent deacetylase (sirtuin 1) promotes axonal elongation, neurite outgrowth, and dendritic branching. Sirtuin 1 plays a relevant protective role in PD [82, 83] |
| ZFP112 | 19 | 8 | Zinc finger protein 112 homolog |
| SHC4 | 18 | 5 | SHC (Src homology 2 domain containing) family, member 4 (aliase ShcD), interacts with tropomyosin receptor kinase B, trkB [84], the high affinity receptor for BDNF expressed in striatal neurons. BNDF can reverse neuronal injury associated with PD [85] |
| TMEM123 | 18 | 0 | Transmembrane protein 123, a cell surface receptor mediating oncotic cell death [86]. Oncosis may be triggered by oxidative stress [87] and is important for neuronal homeostasis [88] |
| BCKDHB | 17 | 17 | Branched chain keto acid dehydrogenase E1, beta polypeptide, a multienzyme complex associated with the inner membrane of mitochondria, functioning in the catabolism of branched chain amino acids. BCKDHB is essential for glutathione homeostasis [89, 90] |
| CBFB | 17 | 4 | Core-binding factor, beta subunit, is a transcription factor that plays critical roles in neuron development [91, 92] |
| CLDND1 | 9 | 26 | Claudin 1. Claudin-family proteins are involved in tight-junction formation at the blood-brain barrier (Luissint et al., 2012 [78]) and CLDN1 is expressed in the substantia nigra compacta [93] |
| GLDN | 3 | 22 | Gliomedin (Gldn) secreted by Schwann cell microvilli binds NgCAM-related CAM (NrCAM) and neurofascin-186 (NF186); it mediates heterotypic cell-cell adhesion [94, 95] |
| MBTD1 | 11 | 21 | Member of the Polycomb group (PcG) protein family. It binds the Rb-E2F complex and contributes to cell cycle progress and apoptosis [96, 97] |
| ARID4B | 6 | 19 | Chromatin remodeling gene coding for a protein associated with mSIN3A histone deacetylase complex [98]. It is involved in neuronal apoptosis [99] |
| HNRNPA3 | 6 | 18 | Shuttling RNA transporter found in neuronal RNA granules and P-bodies [100] |
| SORT1 | 15 | 16 | Sortilin 1 is a member of the family of vacuolar protein sorting 10 protein domain receptors. It is a coreceptor in cell death and neurodegeneration processes mediated by proneurotrophins [101, 102]; it contributes to neuronal apoptosis or neurodegeneration during pathogenesis and progression of Parkinson's disease [103]. |
*Bold numbers indicate highly linked hubs in CT and or PD networks.