Ferroptosis-related factors in the substantia nigra are associated with Parkinson's disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37717088", "kind": "science-record", "revision": 4, "content_hash": "sha256:934303cb220f2fb4d58dc5bc0a4547cbaf2c753452fd4ef7751a7f4b672742f4", "created_at": "2026-11-01T19:02:32Z", "updated_at": "2026-11-01T22:10:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis-related factors in the substantia nigra are associated with Parkinson's disease.", "doi": "10.1038/s41598-023-42574-4", "pmid": "37717088", "authors": ["Lei Liu", "Yange Cui", "Yan-Zhong Chang", "Peng Yu"], "journal": "Scientific reports", "year": 2023, "abstract": "Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death pathway, while Parkinson's disease (PD) patients exhibit iron deposition and lipid peroxidation in the brain. Thus, the features of ferroptosis highly overlap with the pathophysiological features of PD. Despite this superficial connection, the possible role(s) of ferroptosis-related (Fr) proteins in dopaminergic neurons and/or glial cells in the substantia nigra (SN) in PD have not been examined in depth. To explore the correlations between the different SN cell types and ferroptosis at the single-cell level in PD patients, and to explore genes that may affect the sensitivity of dopaminergic neurons to ferroptosis, we performed in silico analysis of a single cell RNA sequence (RNA-seq) set (GSE178265) from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in the different cell types in the human SN, and proceeded to perform enrichment analysis, constructing a protein-protein interaction network from the DEGs of dopaminergic neurons with the Metascape database. We examined the intersection of Fr genes present in the FerrDb database with DEGs from the GSE178265 set to identify Fr-DEGs in the different brain cells. Further, we identified Fr-DEGs encoding secreted proteins to implicate cell-cell interactions in the potential stimulation of ferroptosis in PD. The Fr-DEGs we identified were verified using the bulk RNA-seq sets (GSE49036 and GSE20164). The number of dopaminergic neurons decreased in the SN of PD patients. Interestingly, non-dopaminergic neurons possessed the fewest DEGs. Enrichment analysis of dopaminergic neurons' DEGs revealed changes in transmission across chemical synapses and ATP metabolic process in PD. The secreted Fr-DEGs identified were ceruloplasmin (CP), high mobility group box 1 (HMGB1) and transferrin (TF). The bulk RNA-seq set from the GEO database demonstrates that CP expression is increased in the PD brain. In conclusion, our results identify CP as a potential therapeutic target to protect dopaminergic neurons by reducing neurons' sensitivity to ferroptosis.", "claims": [{"id": "claim-method", "statement": "DEG analysis was performed using the ‘wilcox’ algorithm with a logfc.threshold value of 0.4.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37717088", "locator": "sections[4] \"Cell type annotation and DEGs analysis\" paragraph 2", "quote": "DEG analysis was performed using the ‘wilcox’ algorithm with a logfc.threshold value of 0.4."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets [GENERATED] for this study can be found in the [GEO DATABASE] [https://www.ncbi.nlm.nih.gov/geo/].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37717088", "locator": "sections[20] \"Data availability\" paragraph 2", "quote": "The datasets [GENERATED] for this study can be found in the [GEO DATABASE] [https://www.ncbi.nlm.nih.gov/geo/]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The bulk RNA-seq set from the GEO database demonstrates that CP expression is increased in the PD brain.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37717088", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The bulk RNA-seq set from the GEO database demonstrates that CP expression is increased in the PD brain."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The bulk RNA-seq set from the GEO database demonstrates that CP expression is increased in the PD brain.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37717088"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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