Amphiregulin blockade decreases the levodopa-induced dyskinesia in a 6-hydroxydopamine Parkinson's disease mouse model.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37101388", "kind": "science-record", "revision": 4, "content_hash": "sha256:a120179607ab75df97ff8bfe0d718674501068c690516b0bf7cff319f2ccb49d", "created_at": "2026-11-01T19:01:46Z", "updated_at": "2026-11-01T22:51:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Amphiregulin blockade decreases the levodopa-induced dyskinesia in a 6-hydroxydopamine Parkinson's disease mouse model.", "doi": "10.1111/cns.14229", "pmid": "37101388", "authors": ["Piniel Alphayo Kambey", "Wen Ya Liu", "Jiao Wu", "Chuanxi Tang", "Wokuheleza Buberwa", "Adonira Saro", "Alphonce M K Nyalali", "Dianshuai Gao"], "journal": "CNS neuroscience & therapeutics", "year": 2023, "abstract": "BACKGROUND: Levodopa (L-DOPA) is considered the most reliable drug for treating Parkinson's disease (PD) clinical symptoms. Regrettably, long-term L-DOPA therapy results in the emergence of drug-induced abnormal involuntary movements (AIMs) in most PD patients. The mechanisms underlying motor fluctuations and dyskinesia induced by L-DOPA (LID) are still perplexing.\nMETHODS: Here, we first performed the analysis on the microarray data set (GSE55096) from the gene expression omnibus (GEO) repository and identified the differentially expressed genes (DEGs) using linear models for microarray analysis (Limma) R packages from the Bioconductor project. 12 genes (Nr4a2, Areg, Tinf2, Ptgs2, Pdlim1, Tes, Irf6, Tgfb1, Serpinb2, Lipg, Creb3l1, Lypd1) were found to be upregulated. Six genes were validated on quantitative polymerase chain reaction and subsequently, Amphiregulin (Areg) was selected (based on log2 fold change) for further experiments to unravel its involvement in LID. Areg LV_shRNA was used to knock down Areg to explore its therapeutic role in the LID model.\nRESULTS: Western blotting and immunofluorescence results show that AREG is significantly expressed in the LID group relative to the control. Dyskinetic movements in LID mice were alleviated by Areg knockdown, and the protein expression of delta FOSB, the commonly attributable protein in LID, was decreased. Moreover, Areg knockdown reduced the protein expression of P-ERK. In order to ascertain whether the inhibition of the ERK pathway (a common pathway known to mediate levodopa-induced dyskinesia) could also impede Areg, the animals were injected with an ERK inhibitor (PD98059). Afterward, the AIMs, AREG, and ERK protein expression were measured relative to the control group. A group treated with ERK inhibitor had a significant decrease of AREG and phosphorylated ERK protein expression relative to the control group.\nCONCLUSION: Taken together, our results indicate unequivocal involvement of Areg in levodopa-induced dyskinesia, thus a target for therapy development.", "claims": [{"id": "claim-method", "statement": "In order to ascertain the differentially expressed genes associated with levodopa‐induced dyskinesia, analysis of GSE55096 data set was done using the LIMMA package from Bioconductor.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37101388", "locator": "sections[15] \"Analysis of the microarray data set (GSE55096) using LIMMA informs 12 differentially upregulated genes involved in levodopa‐induced dyskinesia\" paragraph 2", "quote": "In order to ascertain the differentially expressed genes associated with levodopa‐induced dyskinesia, analysis of GSE55096 data set was done using the LIMMA package from Bioconductor."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data that were gathered or evaluated during the course of the investigation are included in this article. The data that support the findings of this study are available in Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55096, reference number GSE55096. These data were derived from the following resources available in the public domain: GEO, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55096.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37101388", "locator": "sections[28] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Data that were gathered or evaluated during the course of the investigation are included in this article. The data that support the findings of this study are available in Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55096, reference number GSE55096. These data were derived from the following resources available in the public domain: GEO, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55096."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LIMMA analysis of the GEO microarray dataset GSE55096 identified 12 upregulated genes, among which Areg was selected for further investigation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37101388", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Here, we first performed the analysis on the microarray data set (GSE55096) from the gene expression omnibus (GEO) repository and identified the differentially expressed genes (DEGs) using linear models for microarray analysis (Limma) R packages from the Bioconductor project. 12 genes (Nr4a2, Areg, Tinf2, Ptgs2, Pdlim1, Tes, Irf6, Tgfb1, Serpinb2, Lipg, Creb3l1, Lypd1) were found to be upregulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "LIMMA analysis of the GEO microarray dataset GSE55096 identified 12 upregulated genes, among which Areg was selected for further investigation.", "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:37101388"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE55096"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE55096"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37101388", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/cns.14229", "sha256": "sha256:45213e254f813c630fd3efcabf067098d14268f24380bba5be5f8396601f1e6c", "bytes": 50098, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/cns.14229", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10493657", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE55096", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55096", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55096", "version": null, "note": "Data that were gathered or evaluated during the course of the investigation are included in this article. 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Dyskinetic movements in LID mice were alleviated by Areg knockdown, and the protei", "rain First, we induced a Parkinson's disease mouse model by stereotaxically injecting 6‐hydroxydopami", "hydroxydopamine (6‐OHDA) Parkinson's disease mouse model. After a preliminary bioinformatics analysis"], "order_basis": "paper_text_order:62", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Here, we first performed the analysis on the microarray data set (GSE55096) from the gene expression", "pressed genes (DEGs) using linear models for microarray analysis (Limma) R packages from the Biocond", "ere regarded as significant. Analysis of the microarray data set (GSE55096) using LIMMA informs 12 d"], "order_basis": "paper_text_order:497", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["therapeutic role in the LID model. RESULTS: Western blotting and immunofluorescence results show that ARE", "stration of the study. The behavior test and western blot were done after 2,4,6,8, and 10 weeks post t", "ure 3D, p = 0.0001, t = 29.37, df = 10). The western blotting results indicate a reduced Tyrosine hydroxyl", "ontralateral rotation (D) were analyzed. The western blot analysis revealed that the marker of dopamin"], "order_basis": "paper_text_order:1161", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["the LID model. RESULTS: Western blotting and immunofluorescence results show that AREG is significantly expr"], "order_basis": "paper_text_order:1181", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ovements in LID mice were alleviated by Areg knockdown, and the protein expression of delta FOSB, t", "rotein in LID, was decreased. Moreover, Areg knockdown reduced the protein expression of P-ERK. In"], "order_basis": "paper_text_order:1349", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["In order to ascertain the differentially expressed genes associated with levodopa‐induced dyskinesia, analysis of GSE55096 data set was done using the LIMMA package from Bioconductor."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}