Table 1. Differentially Expressed Genes (DEGs): α-syn vs. α-syn + Δsid-1.
| Gene | log2Fold Change | P value (adjusted) | Human Ortholog(s) | Function / Disease Relevance |
|---|---|---|---|---|
| Downregulated in Δsid-1 + α-syn | ||||
| vms-1 | 2.50 | 3.6E-177 | ANKZF1 | Linked to prevention of proteotoxic stress by freeing stalled ribosomes [38] |
| E04F6.4 | 2.20 | 2.63E-12 | PLD3-5 | detect foreign nucleic acids and participate in immune inflammation; PLD3 LOF tied to AD [39]; PLD4 tied to microglial activation [40] |
| dop-4 | 3.12 | 7.78E-11 |
HTR1A;
D3R |
dopamine receptor in C. elegans; biogenic amine dysfunction; generalized anxiety disorder; periodic fever; Parkinson’s disease, dyskinesia |
| ugt-36 | 3.38 | 5.42E-5 |
UGT1A1,3–7, 8,9,10;3A1,2 UGT2A1 |
metabolic enzymes; a UGT was associated with detoxification of α-synucleinopathy in PD [41] |
| F49C12.6 | 2.46 | 1.80E-5 | TMEM144 | transport of carbohydrates across membrane; linkage found to Lewy body dementia [42] |
| Upregulated in Δsid-1 + α-syn | ||||
| Y39B6A.27 | 3.20 | 1.04E-68 | MFSD11 | Uncharacterized neuronal solute carrier/transporter |
| fmo-3 | 2.29 | 1.49E-14 | FMO1-5 | Oxidoreductases linked to drug metabolism; linked to neuroprotection [43] |
| clec-210 | 3.50 | 9.00E-9 | REG1A | carbohydrate binding; regulates cell migration; affects innate immunity and apoptosis |
| Y39B6A.29 | 3.12 | 9.66E-9 | MFSD11 | Uncharacterized neuronal solute carrier/transporter |
| pgp-7 | 3.13 | 6.71E-8 | ABCB1,4,5,11 | ATP-binding transmembrane transporter; inhibits xenobiotics entry via gut or across blood/brain barrier; linked to autoimmune disorders and cancers [44] |
| his-11 | 4.2 | 9.62E-8 | H2BC18 | Nucleosome component |
| his-25 | 2.46 | 2.67E-6 | H3C15 | Nucleosome component |
| clec-4 | 2.75 | 1.12E-5 |
TLL1. CLEC3A, B |
Calcium-dependent carbohydrate binding; associated with innate immunity and cell adhesion; CLEC3B mouse knockouts have PD symptoms [45] |
| ech-1.1 | 2.03 | 7.64E-5 | HADHA | Enzymes involved in catabolism of fatty acids; deficiency linked to mitochondrial dysfunction [46]; implicated in AD |
| clec-52 | 2.89 | 1.56E-4 |
CD302; PLA2R1; MRC1,2 |
Carbohydrate binding; associated with innate immunity, microglia phagocytosis, antigen processing; PLA2R1 induces senescence by promoting ROS accumulation [47]; MRC1 expression inversely related to PD in a mouse model through altered microglial activity [48] |
| hmit-1.1 | 2.30 | 5.04E-4 | SLC2A13 | Proton/myo-inositol symporter expressed in human brain; GWAS-identified mutation in SLC2A13 linked to PD [49] |
| col-159 | 2.74 | 0.0017 |
COL6A5
MARCO |
human macrophage receptor, implicated in amyloid-beta binding; linked to AD by amyloid-beta clearance and neuroinflammation mediated by glial cells [50] |
| daf-6 | 2.27 | 0.0021 | PTCHD1,3,4 | transcriptional regulator: null mutants exhibit dysfunctions in neuron mediated behavior; mutations in PTCHD1 linked to autism and other cognitive disorders due to disruptions to synaptic function [51] |
| pgp-8 | 2.07 | 0.0026 | ABCB1,4,5,11 | ATP-binding transmembrane transporter; inhibits xenobiotics entering body via gut or crossing blood/brain barrier; implicated in autoimmune diseases and cancers [44] |
| col-150 | 2.32 | 0.0043 | SFTPD | Surfactant in human respiratory function/innate immunity; Implicated in inflammation [52] |
| kin-15 | 2.36 | 0.0067 |
FLT3; KIT; PDGFRA, B; CSF1R |
Membrane receptor kinase: human orthologs exhibit very diverse functions; implicated in multiple cancers |
| W01B6.3 | 2.68 | 0.0081 | MFSD8 | Lysosomal transporter: mutations in MFSD8 cause a heritable neurodegenerative disorder characterized by accumulation of lysosomal storage materials [53] |
| F49E12.10 | 2.49 | 0.0097 | FAXDC2 | Oxidoreductase with predicted fatty acid modification; FAXDC2 tied to differentiation of platelet-generating marrow cells; blood RNA levels of FAXDC2 exhibit efficacy as a PD biomarker [54] |
| W07B8.4 | 2.21 | 0.0105 | CTSB | Lysosomal protease; associated with promoting oxidative stress and microglial neuroinflammation [55]; decreased levels have been associated with exacerbating glucocerebrosidase dysfunction and overall PD risk [56] |
| C55C3.4 | 4.82 | 0.0112 | FER, FES | non-membrane bound tyrosine kinase; mediates responses of innate immune pathways and growth factors in humans |
| H39E23.3 | 2.28 | 0.0125 |
SON;
NEFH; CLIC6 |
microtubule binding in worm DA neurons; NEFH is an intermediate filament component of the neuronal cytoskeleton; CLIC6 is an intracellular chloride channel associated with regulation of D2-like receptors; NEFH was identified by whole exome sequencing of PD patient DNA [57] |
| his-16 | 3.79 | 0.0487 | H2AC21 | Nucleosome component |