Table 1. H1N1+Mn unique genes relevant to neurodegeneration.
| Genes | Protein Product description | Pathway of Interest | References |
|---|---|---|---|
| Park7 | Parkinson disease (autosomal recessive, early onset) 7; Protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins and releases repaired proteins and lactate or glycolate, respectively. | SUMOylation of transcription cofactors | [59–62] |
| Lingo2 | Leucine rich repeat and Ig domain containing 2. Genetic polymorphisms in LINGO1 and LINGO2 associated with increased risk of developing essential tremor and Parkinson Disease (PD). Lingo (1,2) is an axonal inhibitor. | Axonal growth inhibition (RHOA activation) | [56, 57, 63] |
| Pak6 | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. May protect cells from apoptosis through phosphorylation of BAD. | Activation of RAC1 | [64–66] |
| Eif2c1 | Eukaryotic translation initiation factor 2C1; Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Recent evidence indicates that small RNAs participate in transcriptional regulation in addition to post-transcriptional silencing and damage repair. | Regulation of pTEN mRNA translation | [67–76] |
| Keap1 | Kelch-like ECH-associated protein 1; Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. | Ub-specific processing proteases | [77–80] |
| Sox11 | Transcriptional factor involved in the embryonic neurogenesis. May also have a role in tissue modeling during development. | Binding of chemokine receptors | [81–84] |
| Sox13 | Member of SOX family of transcription factors. | Binding of chemokine receptors | [81–84] |
| Arc | Activity regulated cytoskeletal-associated protein; Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics, cell migration, consolidation of synaptic plasticity and formation of long-term memory. | Trafficking of AMPA receptors | [85–87] |
| Iigp1 | GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Mediates resistance to infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction. | Resistance to infection. | [88] |
| Camk1 | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. | Transcriptional activation of mitochondrial biogenesis. | [89–91] |
| Slc30a4 | Likely involved in zinc transport out of the cytoplasm, perhaps be by sequestration into an intracellular compartment. | Zinc efflux | [92–94] |
| Atg9a | Involved in autophagy and cytoplasm to vacuole transport (Cvt) vesicle formation. Plays a key role in the organization of the preautophagosomal structure/phagophore assembly site (PAS), the nucleating site for formation of the sequestering vesicle. | Macroautophagy | [95–98] |
| Per1 | Transcriptional repressor that forms a core component of the circadian clock. | Circadian clock | [99–103] |
| Gabra2 | Gamma-aminobutyric acid (GABA) A receptor, subunit alpha 2; GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | Neurotransmitter receptors and postsynaptic signal transmission | [99–103] |
| Gabra5 | Gamma-aminobutyric acid (GABA) A receptor, subunit alpha 5; GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | Neurotransmitter receptors and postsynaptic signal transmission | [104–106] |
| Ildr2 | Immunoglobulin-like domain containing receptor 2; May be involved in ER stress and lipid homeostasis. | ER stress pathway | [107–110] |
| Tcf3 | Transcription factor 3; Transcriptional regulator. Involved in the initiation of neuronal differentiation. Heterodimers between TCF3 and tissue- specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. | CDO (cell-adhesion-molecule/downregulated by oncogenes) in myogenesis | [111] |
| Map4k4 | Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. | Oxidative stress induced senescence | [112–121] |
PANTHER overrepresentation analysis was used to more narrowly identify unique genes relevant to neurodegeneration. Results with FDR<0.05 and an enrichment score >1.5 were considered significant. From among statistically significant GO Terms, genes annotated to those categories were selected according to relevance to neurodegeneration.