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

Table 3

Main hubs in LC-CT and LC-PD networks^*.

Gene	Gene-gene links		Gene product and/or biological function
	CT	PD
GPRC5B	30	6	Orphan G protein-coupled receptor (putative glutamate receptor candidate) required for neuronal differentiation [45]
GRM3	23	4	Group II metabotropic glutamate receptor modulating glutamate neurotransmission and synaptic plasticity. It plays a role in neuroprotection and white matter integrity [46–48]
UGT8	23	1	UDP glycosyltransferase 8. Highly expressed in brain oligodendrocytes. Involved in myelination and maintenance of white matter tracts within the central nervous system [49, 50]
NUDT13	21	23	Mitochondrial enzyme (Nudix hydrolase) involved in response to oxidative stress [51]
SEPP1	21	1	Selenoprotein P, plasma, 1. Maintains selenium homeostasis in the brain. Involved in antioxidant protection of astrocytes and neurons [52]
RGS5	20	25	Regulator of G protein signaling 5. It is a marker of brain pericytes [53]
PCOLCE2	20	5	Procollagen C-endopeptidase enhancer 2 [54]. It regulates apoAI posttranslational processing [55]
PPP4R1	4	40	Protein phosphatase 4 catalytic unit [56]
FAM5B	12	35	BRINP2 (aliase). BMP/RA-inducible neural specific protein. BRINP1, BRINP2, and BRINP3 are predominantly and widely expressed in both the central nervous system (CNS) and the peripheral nervous system (PNS) and involved in neuron development [57]
MED30	17	32	Mediator of RNA polymerase II transcription subunit 30. Required for oxidative phosphorylation and mitochondrial integrity [58]
TOB2	11	29	TOB2 regulates mRNA deadenylation, potentiates NGF-induced differentiation, and protects neurons from apoptosis [59, 60]
ZNRF3	11	29	ZNRF3 promotes Wnt receptor turnover [61]. Wnt signaling is linked to synaptic maintenance in the aging brain [62] and regulation of inflammatory pathways along PD progression [63]
PARP4	3	29	Poly-ADP-ribose polymerase controlling synaptic plasticity via major vault protein [64]
ATXN1	12	28	Polyglutamine-containing protein. Polyglutamine (polyQ) disease gene putatively involved in autosomal dominant Parkinson’s disease [65]
SFRS18	3	28	Serine-arginine rich protein (aliase SF2/AFS) regulates protein sumoylation [66]. Protein sumoylation inhibits alfa-synuclein aggregation and toxicity [67]
GAS7	10	26	Growth arrest-specific gene 7 (Gas7) is involved in neurite outgrowth and motor neuron function [68, 69]

Bold numbers indicate highly linked hubs in CT and or PD networks.