Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences.

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The thermodynamic stability profiles generated here on 332 proteins were compared to thermodynamic stability profiles generated on the same proteins from similarly aged wild-type mice using a two-way unbalanced analysis of variance (ANOVA) analysis. This analysis identified a group of 22 proteins with age-related protein stability changes and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model. A total of 9 of the 11 proteins identified here with disease-related stability changes have been previously detected in human cerebral spinal fluid and thus have potential utility as biomarkers of Parkinson's disease (PD). The differential stability observed for one protein, glutamate decarboxylase 2 (Gad2), with an age-related change in stability, was consistent with the differential presence of a known, age-related truncation product of this protein, which is shown here to have a higher folding stability than full-length Gad2. Mass spectrometry data were deposited at ProteomeXchange (PXD016985).", "claims": [{"id": "claim-method", "statement": "For each methionine-containing peptide, a two-way unbalanced ANOVA test was employed to identify significant differences between the assigned C1/2 values across the 6 groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34606284", "locator": "sections[8] \"Identification of Differentially Stabilized Proteins\" paragraph 2", "quote": "For each methionine-containing peptide, a two-way unbalanced ANOVA test was employed to identify significant differences between the assigned C1/2 values across the 6 groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw LC-MS/MS data and search outputs, can be found at the ProteomeXchange Consortium via the Pride repository with the identifier PXD016985.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34606284", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The raw LC-MS/MS data and search outputs, can be found at the ProteomeXchange Consortium via the Pride repository with the identifier PXD016985."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This analysis identified a group of 22 proteins with age-related protein stability changes, and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34606284", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This analysis identified a group of 22 proteins with age-related protein stability changes, and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This analysis identified a group of 22 proteins with age-related protein stability changes, and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model.", "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:34606284"], "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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