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. 2024 Apr 1;15:2823. doi: 10.1038/s41467-024-47028-7

Fig. 8. PV-IN-specific decrease in mTOR signaling in early Aβ pathology.

Fig. 8

A. Akt/mTOR and/or MAPK signaling proteins biotinylated in PV-IN CIBOP proteomes (as compared to non-CIBOP mice). B. Akt/mTOR and MAPK proteins identified as DEPs comparing 5xFAD to WT PV-IN proteomes. C. Heatmap representation of Akt/mTOR and MAPK DEPs in PV-IN proteomes and their corresponding bulk brain proteomes (*p < 0.05, two-tailed unpaired T-test). D. Cartoon representation of adapted Luminex immunoassay to measure levels of PV-IN-derived phospho-proteins belonging to Akt/mTOR and MAPK proteins from bulk tissue. E. Heatmap visualization of Akt/mTOR and MAPK phospho-proteins in PV-INs measured by adapted Luminex assay from WT and 5xFAD mice (n = 3 mice/group, p < 0.05 unpaired two-tailed T-test). F. Summary: Decreased activity in mTOR signaling in 5xFAD PV-INs as compared to WT PV-INs, based on total protein levels estimated by PV-CIBOP MS, and phospho-protein levels by the adapted Luminex approaches. G. Comparison of proteins that positively regulate autophagy (GO:0010508), in 5xFAD and WT PV-IN proteomes (protein levels were normalized, z-transformed and then group-averaged across biological replicates before group comparisons; unpaired two-tailed T-test,*p < 0.05). H. Top: WB of PV-IN (SA-enriched) samples from 5xFAD and WT PV-CIBOP brain. LC3-II/I ratio was compared across the two groups. Bottom: Biotinylated protein from samples corresponding to WB images above. Data are displayed as mean values +/- SEM. (n = 3 (WT), 4 (5xFAD), *p < 0.05, independent two-tailed T-test). I. Analysis of DEPs (5xFAD vs. WT PV-IN proteomes) based on published protein half-lives in mouse brain. Proteins with increased levels in 5xFAD PV-INs were skewed towards proteins with longer half-lives ( > 13.7 days which represents the 75th percentile of protein half-lives in brain). This pattern is consistent with decreased translational efficiency and/or increased protein degradation, which would disproportionately impact the relative abundances of short-lived proteins. J. Comparison of proteins that regulate synaptic plasticity (GO:0048167) as a group, in 5xFAD and WT PV-IN proteomes (levels of 102 proteins were normalized, z-transformed and then averaged across biological replicates before group comparisons using unpaired two-tailed T-test (***p < 0.005). See Supplementary Data 6 for related analyses. Source data are provided as a Source Data file.