FIG 6.

Augmented ERVK RT levels in ALS cortical neurons correlate with enhanced nuclear localization of proinflammatory transcription factors. (A) The mean optical intensity (relative intensity) was used as a metric to quantify the level of total ERVK RT, as well as the level of nuclear IRF1, NF-κB p50, or NF-κB p65, in cortical neurons from neuronormal individuals (n = 86 cells [10 to 29 cells per case]) and patients with ALS (n = 105 cells [10 to 27 cells per case]). Clinical groups (n = 5 each) were compared using the nonparametric Mann-Whitney U test. The expression of total ERVK RT and nuclear translocation of each transcription factor increased significantly in ALS cortical neurons compared to the controls (***, P < 0.0001). (B) Pearson's correlation between the mean relative intensities of total ERVK RT and nuclear IRF1, NF-κB p50, or NF-κB p65 measured in neuronormal (NN) (red) and ALS (blue) cortical neurons. ERVK RT expression exhibited a moderate (p65 [0.6863]) to strong (IRF1 [0.8574] and p50 [0.8405]) correlation with the extent of nuclear localization for each transcription factor. (C) ROC curve analyses depicting the accuracy (area under the curve [AUC]) of augmented ERVK RT and proinflammatory transcription factor levels in discriminating between cortical neurons in controls and those in ALS tissues. IRF1 and NF-κB p50 levels were excellent predictors of ALS. In contrast, total ERVK RT and nuclear NF-κB p65 levels were less accurate at distinguishing between the normal and diseased states.