Fig. 4 | Nature Communications

Fig. 4

From: HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons

Fig. 4The alternative text for this image may have been generated using AI.

Global analysis of proteins and protein networks enriched in response to PD-relevant genetic and toxic stress in hPSC-derived mDA neurons. a Schematic illustration of the experimental design for chemoproteomic studies and the identification and validation of proteins and protein pathways enriched in S-HSP90 complexes under each PD stress. See Supplementary Data 1–4 for protein lists, statistical analyses and results of Reactome and GO enrichment analyses. b Heatmap of S-HSP90 bound proteins indicating those significantly enriched in mDA neurons under genetic (Parkin defect) stress. c Important cellular functions and pathways enriched under genetic stress. Inset shows the enrichment in inflammatory and signaling-related processes, with those incorporating STAT3 and NF-kB/p65-related pathways circled in red. (CCCP; 10 µM; rotenone; 20 nM). d Western blot confirms an increase in STAT3 and NF-kB/p65-activity in PD over WT mDA neurons, irrespective of the additional toxic stress. Mean ± SEM, n = 3 individual values from the different experiments shown as points, t-test, ***p < 0.001; **p < 0.01

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