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Fig. 2 | Alzheimer's Research & Therapy

Fig. 2

From: The hibernation-derived compound SUL-138 shifts the mitochondrial proteome towards fatty acid metabolism and prevents cognitive decline and amyloid plaque formation in an Alzheimer’s disease mouse model

Fig. 2

Proteomic analysis of SUL-138 treatment in APP/PS1 and wildtype mice. A Following 3 months of vehicle (VEH) or SUL-138 (SUL) treatment of wildtype (WT) and APP/PS1 mice (n = 6 per group), hippocampal P2 protein samples were prepared, FASP-digested, and used for quantitative DIA mass spectrometry. In total, 7486 proteins were measured. Data was further analyzed using gene ontology (GO) enrichment for cellular components (CC) and biological processes (BP) against the GO, SynGO, and MitoXplorer databases. B Differential protein expression was determined for three contrasts, APP VEH vs. WT VEH (blue), APP SUL vs. APP VEH (purple), and WT SUL vs. WT VEH (orange), resulting in the indicated numbers of significant differentially expressed proteins (FDR, q ≤ 0.05). C In the APP VEH vs. WT VEH comparison, most proteins are significantly downregulated (365 down vs. 184 up, FDR q ≤ 0.05) in APP/PS1 mice. Proteins that are dysregulated in APP/PS1 and are regulated in SUL treated APP/PS1 or WT are highlighted in red when they are upregulated and blue when they are downregulated in APP VEH vs. WT VEH. F In the APP VEH vs. APP SUL comparison, most proteins are significantly upregulated (109 up vs. 42 down, FDR q ≤ 0.05) after SUL-138 treatment. Proteins that are dysregulated in APP/PS1 are highlighted in red when they are upregulated and blue when they are downregulated in APP VEH vs. WT VEH to illustrate directionality of SUL-138 regulation. I In the WT VEH vs. WT SUL comparison, most proteins are significantly upregulated (60 up vs. 17 down, FDR q ≤ 0.05) after SUL-138 treatment. Proteins that are dysregulated in APP/PS1 and are regulated in SUL treated WT are highlighted in red (upregulated in APP VEH vs. WT VEH) and blue (downregulated in APP VEH vs. WT VEH) to illustrate directionality of SUL-138 regulation. D, E, G, H, J Top 10 enriched CC GO terms for upregulated (top panel) and downregulated (lower panel) proteins for each of the 3 contrasts. Size of the dots represents the number of proteins annotated to the GO term and the fraction of significant proteins is the number of significant proteins divided by the total number of proteins belonging to that term

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Alzheimer's Research & Therapy

ISSN: 1758-9193