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Fig. 4 | Cellular & Molecular Biology Letters

Fig. 4

From: APOE2 protects against Aβ pathology by improving neuronal mitochondrial function through ERRα signaling

Fig. 4

ApoE2 interacts with ERRα. a SCENIC analysis of different transcription factors (TFs) activity between APOE2 versus APOE3 neurons under AD pathology (adjusted. P value < 0.05). b The predicted target genes of ESRRA. c The distribution of ESRRA gene expression in dorsolateral prefrontal cortex (DLPFC). d Co-localization of the ERRα protein (green) with the neuronal marker NeuN (red) in mouse cortex. Scale bars, 100 μm for low magnification, 25 μm for high magnification. e Co-localization of the ERRα protein (green) with ApoE (red) in mouse cortex. Scale bars, 100 μm for low magnification, 25 μm for high magnification. f, g Binding mode of ApoE2 (e) or ApoE3 (f) and ERRα predicted by HDOCK. Left: overall structure of ApoE2 or ApoE3 bound to ERRα in cartoon view. ApoE2, ApoE3, and ERRα were colored in pink, dark green, and orange, respectively. Right: detailed interaction network between ApoE2 or ApoE3 and ERRα. Key residues of ApoE2 (pink) or ApoE3 (green) and ERRα (orange) were displayed as sticks. H-bonds are displayed in black dashed lines, and the distances (acceptor to donor heavy atom) of H-bonds are labeled. h, i Co-IP indicating the direct bind of ERRα protein and ApoE2 protein in HEK-293 T cells (h) and hAPOE2-TR mouse cortex (i). j Representative immunoblotting images of ERRα protein expression after APOE2 or APOE3 plasmid transfection and Aβ1-42 stimulation. Data were presented as the mean ± S.E.M. The experiment had three independent biological replicates (One-way ANOVA); *P < 0.05; **P < 0.01. k The correlation between ESRRA activity and CERAD pathology between APOE genotypes in Ex-PYR neurons (APOE2: R = 0.0073, P = 0.88; APOE3: R = 0.14, P = 0.00053). A significant difference between these two groups was confirmed through Cocor (Z = -2.1449, P = 0.0320); *P < 0.05. l The correlation between ESRRA activity and CERAD pathology between APOE genotypes in In-PV (Basket) neurons (APOE2: R = -0.053, P = 0.3; APOE3: R = 0.11, P = 0.023). A significant difference between these two groups was confirmed through Cocor (Z = -2.2957, P = 0.0217); *P < 0.05

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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