Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

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.