Abnormal　accumulation　of　alpha　synuclein　(α-Syn)　in　sporadic　and　familial　Parkinson’s　disease　(PD)　may　be　a　key　step　in　its　pathogenesis.　In　this　study,　the　expression　matrix　of　the　GSE95427　dataset　after　α-Syn　overexpression　in　human　glioma　cell　line　H4　was　obtained　from　the　GEO　database.　We　used　the　Gene　Set　Enrichment　Analysis　(GSEA)　method　to　reanalyze　this　dataset　to　evaluate　the　possible　functions　of　α-Syn.　The　results　showed　that　the　tumor　necrosis　factor　alpha　(TNF-α)　signal　was　significantly　activated　in　α-Syn-overexpressing　cells,　and　oxidative　phosphorylation　signal,　extracellular　matrix　signal,　cell　cycle　related　signal　and　fatty　acid　metabolism　signal　were　significantly　inhibited.　Moreover,　we　employed　the　α-Syn-expressing　transgenic　Drosophila　model　of　Parkinson’s　disease　and　knocked-down　eiger,　a　TNF　superfamily　ligand　homologue,　indicating　that　the　TNF-α　pathway　plays　a　role　in　the　common　pathogenesis　of　synucleinopathies.　Our　analysis　based　on　GSEA　data　provides　more　clues　for　a　better　understanding　of　α-Syn　function.　©　2023　by　the　authors.