Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra
Table 2
Main hubs in VA-CT and VA-PD networks.
Gene
Gene-gene links
Gene product and/or biological function
CT
PD
FLYWCH1
23
6
FLYWCH-type zinc finger 1. DNA binding. Involved in transcriptional regulation [25]
HRC
21
4
Histidine rich calcium binding protein. Regulator of homeostasis [26]
S100A4
20
0
S100A4 -binding protein involved in neuroprotection. It rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor [27, 28]
PGM3
19
2
Phosphoglucomutase 3. PGM3 is involved in glycogenolysis and glycogenesis; these processes provide metabolic energy for cellular calcium homeostasis [29] and causes hypomyelination when mutated [30]
SOX10
18
6
Transcription factor. Involved in regulatory network for myelination in oligodendrocytes [31]
CPNE2
18
0
Calcium-dependent membrane binding protein. sensor in postsynaptic events [32]
LOC100128821
17
1
Hypothetical protein LOC100128821
AGBL4
17
0
ATP/GTP binding protein-like 4. CCP6 (aliase). CCP6 catalyzes the shortening of the glutamate side chains, a critical process for neuron survival [33]
IFT88
16
26
Key component of intraflagellar transport and involved in neuron migration and dendrite arborization [34]
ADAM15
11
26
Metalloprotease-disintegrin expressed in brain and involved in neuroprotection [35]
SHARPIN
5
25
Ubiquitin-binding and ubiquitin-like-domain-containing protein. It modulates activation of NF-B signaling pathway and controls cell survival and apoptosis [36–38]
GNL3L
8
24
Guanine nucleotide binding protein-like 3 nucleolar-like, paralogue of nucleostemin (NS). GNL3L, as NS, stabilizes MDM2 protein promoting neuron survival [39, 40]
UBTF
3
24
Upstream binding transcription factor, RNA polymerase I (aliase UBF), is a transcriptional activator regulating rRNA transcription. The activation of the nucleolar transcription is a response to proteotoxic stress in neurons [41]
ARS2
10
21
Ars2 maintains neural stem cell identity via direct transcriptional activation of Sox2 [42]
PLA2G6
2
21
Phospholipase A2, group VI (cytosolic, calcium-independent), PARK14 (aliase). PARK14 gene encodes iPLA2-VIA, a calcium independent phosphatase, catalyzing the hydrolysis of glycerophospholipids. Mutations in this gene can cause autosome recessive early-onset form of PD [43, 44]
