Fig. 6: Histone serine-ADP-ribosylation is decreased in AD brains and cis- and trans-RSV have opposite effects on it.

a HPF1 and histone serine-ADP-ribosylation are decreased in the hippocampal region of AD patients. Representative immunoblots and quantification for HPF1 and histone H3-Ser10-ADP-ribosylation (Serine-ADPR) using anti-HPF1 and anti-H3-Ser10-ADPR antibodies, respectively, in the hippocampal region of AD patients (n = 5) with age and sex-matched controls (n = 5). b Tyrosine decreases the protein levels of HPF1. Representative immunoblots and quantifications for HPF1 in rat cortical neurons (DIV 9/10) after treatment with Tyr (≤300 μM) for up to 8 h for n = 3 experiments. c D-tyrosine inhibits serine-ADP-ribosylation. Representative immunoblots and quantification for histone H3-Ser10-ADP-ribosylation levels in cortical neurons (DIV 9) using anti-H3-Ser10-ADPR antibody after treatment with D-tyrosine (2.5 and 5 mM). d, e cis-and trans-RSV have opposite effects on HPF1 and histone serine-ADP-ribosylation levels. Representative immunoblots and quantification for HPF1 and histone H3-Serine-ADPR using anti-HPF1 and anti-H3-Ser10-ADPR antibodies, respectively in cortical neurons after treatment with cis-and trans-RSV (25–50 μM). f, g BDNF and ISRIB increase HPF1 levels along with the activation of histone serine-ADP-ribosylation. Representative immunoblots and quantification for HPF1 and histone H3-Serine-ADPR using anti-HPF1 and anti-H3-Serine-ADPR antibodies, respectively in cortical neurons after treatment with BDNF (50 nM) and ISRIB (5 and 10 nM). h DA activates histone serine-ADP-ribosylation. Representative immunoblots and quantification for histone H3-Ser10-ADPR levels in cortical neurons (DIV 9) using anti-H3-Ser10-ADPR antibody after treatment with DA (250 μM) for 5–10 min. All data represent mean ± SEM for n = 3 experiments with significance measured using ANOVA with Dunnett’s test for multiple comparisons.