Deficiency of Parkinson's Related Protein DJ-1 Alters Cdk5 Signalling and Induces Neuronal Death by Aberrant Cell Cycle Re-entry.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35182267", "kind": "science-record", "revision": 4, "content_hash": "sha256:aafd3697f4370c4882b42c0cc41c45a598db67add16eebf57a668f8fdd41a030", "created_at": "2026-11-01T17:36:56Z", "updated_at": "2026-11-01T21:27:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deficiency of Parkinson's Related Protein DJ-1 Alters Cdk5 Signalling and Induces Neuronal Death by Aberrant Cell Cycle Re-entry.", "doi": "10.1007/s10571-022-01206-7", "pmid": "35182267", "authors": ["María José López-Grueso", "Carmen Alicia Padilla", "José Antonio Bárcena", "Raquel Requejo-Aguilar"], "journal": "Cellular and molecular neurobiology", "year": 2023, "abstract": "DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase, and transcriptional regulator. However, the exact mechanism by which DJ-1 dysfunction contributes to development of Parkinson's disease remains elusive. Here, using a comparative proteomic analysis between wild-type cortical neurons and neurons lacking DJ-1 (data available via ProteomeXchange, identifier PXD029351), we show that this protein is involved in cell cycle checkpoints disruption. We detect increased amount of p-tau and α-synuclein proteins, altered phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signalling pathways, and deregulation of cyclin-dependent kinase 5 (Cdk5). Cdk5 is normally involved in dendritic growth, axon formation, and the establishment of synapses, but can also contribute to cell cycle progression in pathological conditions. In addition, we observed a decrease in proteasomal activity, probably due to tau phosphorylation that can also lead to activation of mitogenic signalling pathways. Taken together, our findings indicate, for the first time, that aborted cell cycle re-entry could be at the onset of DJ-1-associated PD. Therefore, new approaches targeting cell cycle re-entry can be envisaged to improve current therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Two groups were compared, and statistical analysis of the results was performed by unpaired t test with Welch’s correction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35182267", "locator": "sections[23] \"Statistical Analysis\" paragraph 2", "quote": "Two groups were compared, and statistical analysis of the results was performed by unpaired t test with Welch’s correction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this published article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35182267", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "All data generated or analysed during this study are included in this published article and its supplementary information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:35182267"], "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:PXD029351"], "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:PXD029351"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35182267", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10571-022-01206-7", "sha256": "sha256:293012f0a71b253db2b92db00e14066e53b82071cbf744be0a8e592689e45984", "bytes": 55334, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10571-022-01206-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9958167", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD029351", "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=PXD029351", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD029351", "version": null, "note": "All data generated or analysed during this study are included in this published article and its supplementary information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this published article and its supplementary information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Deficiency of Parkinson´s related protein DJ-1 alters Cdk5 signaling and induces neuronal death by aberrant cell cycle re-entry.", "resolution_checked_at": "2026-11-01T18:06:51Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD029351 not downloaded", "asset:data:geo:PXD029351 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Two groups were compared, and statistical analysis of the results was performed by unpaired t test with Welch’s correction."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["welch_t"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: welch_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD029351"], "resolved_accessions": ["PXD029351"], "statements": ["All data generated or analysed during this study are included in this published article and its supplementary information files."], "basis": "The paper names PXD029351 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["welch_t"], "assets": ["source:pmid:35182267", "data:geo:PXD029351"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD029351"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:34:42Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16525, "completion_tokens": 747, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35182267", "type": "paper", "label": "pmid:35182267"}, {"id": "source:pmid:35182267", "type": "manuscript", "label": "PMID 35182267 full text"}, {"id": "data:geo:PXD029351", "type": "dataset", "label": "GEO PXD029351"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35182267", "type": "paper", "label": "pmid:35182267"}, {"id": "source:pmid:35182267", "type": "manuscript", "label": "PMID 35182267 full text"}, {"id": "data:geo:PXD029351", "type": "dataset", "label": "GEO PXD029351"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35182267", "type": "extraction", "used": ["source:pmid:35182267"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD029351", "type": "accession_resolution", "used": ["data:geo:PXD029351"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35182267", "parent_hash": "sha256:4cf320b833b7dd3997dd1a2ecae59882f954b533d39ce62c1d7a356d19e4a20b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:PXD029351 licence not read", "asset:data:geo:PXD029351 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e remains elusive. Here, using a comparative proteomic analysis between wild-type cortical neurons", "natants were stored at − 80 °C until use for mass spectrometry or Western blot analysis. For the determinat", "pernatants were prepared and analysed in the Proteomics Facility at Research Support Central Service"], "order_basis": "paper_text_order:405", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["hical Statement Regarding the Use of Animals Mice were bred at the Animal Experimentation Unit of t", "anish legislation (RD53/2013). DJ-1-knockout mice were generously donated by Juan P. Bolaños (Unive"], "order_basis": "paper_text_order:1511", "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": ["t − 80 °C until use for mass spectrometry or Western blot analysis. For the determination of proteasom", "PDF 298 kb) Supplementary Figure 3. Original Western Blot images for Fig. 3B. Supplementary Figure 4.", "or Fig. 3B. Supplementary Figure 4. Original Western Blot images for Fig. 3F. Supplementary Figure 5.", "or Fig. 3F. Supplementary Figure 5. Original Western Blot images for Fig. 4D. Supplementary file4 (PDF"], "order_basis": "paper_text_order:2794", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["welch_t"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Two groups were compared, and statistical analysis of the results was performed by unpaired t test with Welch’s correction."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}