Table 3.
Top 20 downregulated genes in α-syn high seeders.
| Gene Symbol | Official Full Name | Representative Pathways in C5 Gene Ontology Set | Reports in LBD or α-Syn | Fold Change (log2) | p-Value | Adjusted p-Value |
|---|---|---|---|---|---|---|
| FASN | Fatty acid synthase | Oxidoreductase activity | None | −0.74 | 0.00022 | 0.347 |
| CCL2 | C-C motif chemokine ligand 2 | Humoral immune response, positive regulation of transmembrane transport | CCL2 promotes α-syn secretion and the neuronal apoptosis induced by α-syn [34]. Correlation with CCL2 and PD clinical stage and autonomic symptom [35]. | −1.82 | 0.00053 | 0.347 |
| ADCY9 | Adenylate cyclase 9 | Adenylate cyclase modulating G protein-coupled receptor signaling | None | −0.626 | 0.00284 | 0.374 |
| RPTOR | Regulatory-associated protein of MTOR complex 1 | Regulation of cell development, negative regulation of autophagy | Association of RPTOR with SNCA and differential age at onset in PD [36]. | −0.417 | 0.00293 | 0.383 |
| ULK1 | Unc-51-like autophagy activating kinase 1 | Cellular response to stress, process utilizing autophagic mechanism | ULK1 increase in LRRK2 PD brains [37]. ULK1 immunoreactivity in LB [38]. ULK1 protein increase in PD blood mononuclear cells [39]. | −0.984 | 0.00319 | 0.383 |
| COL6A1 | Collagen type VI alpha 1 chain | Vacuolar membrane, collagen biding | None | −0.686 | 0.00338 | 0.416 |
| CLSTN1 | Calsyntenin 1 | Postsynaptic membrane, vesicle-mediated transport | CLSTN1 increase in CSF in DLB [40]. | −0.445 | 0.00341 | 0.416 |
| SPTAN1 | Spectrin alpha, non-erythrocytic 1 | Negative regulation of cytoskeleton organization | None | −0.89 | 0.00373 | 0.416 |
| PIK3R2 | Phosphoinositide-3-kinase regulatory subunit 2 | Phosphatidylinositol metabolic process, extrinsic component of membrane | Association with rare variants of PIK3R2 and DLB [41]. | −0.619 | 0.00389 | 0.416 |
| ATP9A | ATPase phospholipid transporting 9A | ATP dependent activity, endosome membrane | None | −0.418 | 0.00402 | 0.416 |
| THBS1 | Thrombospondin 1 | None | LRRK2 mutation promotes ER stress via interacting with THBS1/TGF-β1 in PD [42]. | −2.14 | 0.0041 | 0.416 |
| OLFML3 | Olfactomedin-like 3 | None | None | −0.918 | 0.00448 | 0.416 |
| ATF2 | Activating transcription factor 2 | Regulation of mitochondrial membrane permeability, cellular lipid metabolic process | ATF2 contributes to dopaminergic neurodegeneration in the MPTP mouse model of PD [43]. | −0.341 | 0.00478 | 0.46 |
| EEF2K | Eukaryotic elongation factor 2 kinase | Postsynapse, regulation of dendritic spine morphogenesis | EEF2K increase in PD brain and EEF3K inhibition reduces α-syn toxicity [44]. | −0.711 | 0.00587 | 0.46 |
| PSMC1 | Proteasome 26S subunit, ATPase 1 | Endopeptidase complex, proteasome complex | Depletion of 26S proteasomes in mouse brain causes neurodegeneration and Lewy-like inclusions [45]. | −0.708 | 0.00707 | 0.406 |
| PGAM1 | Phosphoglycerate mutase 1 | Glycolytic process | None | −0.699 | 0.00776 | 0.501 |
| MYD88 | MYD88 innate immune signal transduction adaptor | Stress-activated protein kinase signaling cascade, toll-like receptor 4 signaling | TLR2/MyD88/NF-κB pathway reduces α-syn spreading [46]. | −0.731 | 0.00813 | 0.501 |
| MERTK | MER proto-oncogene, tyrosine kinase | None | MERTK mediates α-syn fibril uptake in microglia [47]. | −0.692 | 0.00868 | 0.501 |
| YWHAG | Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma | Cellular response to insulin stimulus, phosphoprotein binding | YWHAG increase in the SN in PD [48]. | −0.905 | 0.00876 | 0.501 |
| CSF1R | Colony stimulating factor 1 receptor | Neurotransmitter secretion, regulation of leukocyte migration | CSF1R mutation in a case presenting as DLB [49]. | −1.12 | 0.00899 | 0.501 |
Abbreviations: ER: endoplasmic reticulum; LRRK2: leucine-rich repeat serine/threonine-protein kinase 2; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B-cells; SNCA: synuclein alpha; TLR: Toll-like receptor.