Journal: Journal of Alzheimer's disease : JAD

Article Title: Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer’s disease rat model

doi: 10.1177/13872877251314777

Figure Lengend Snippet: RG2833 improves spatial learning and memory in TgF344-AD females. a, b Latency to first entrance during training trials, c latency to second entrance during test trial. d Representative track tracing of individual female performance for trial 6 across treatment conditions. a TGTR females perform significantly better than TGNT females during early acquisition (EA). b WTNT vs WTTR females perform similarly. c Female test data show overall significant improvement in latency to second entrance following RG2833-treatment vs untreated, independent of genotype. No differences were observed in the asymptomatic performance (AP, trials 4–6) across all comparisons (not shown). Repeated measure two-way ANOVA with Sidak’s post hoc tests were used in 2a and 2b. Ordinary two-way ANOVA with Sidak’s post hoc analysis was used in 2c ** P < 0.01, *** P < 0.001. n = 7 WTNT, n = 6 TGNT, n = 13 TGTR, n = 10 WTTR. EA - Early Acquisition; AP – Asymptotic Performance; WTNT – Wild-type not treated; TGNT – transgenic not treated; WTTR – Wild-type RG2833-treated; TGTR – transgenic RG2833-treated; t – trial effect, d – drug effect. For simplicity, error bars are shown in one direction only.

Article Snippet: At 5 months of age TgF344-AD and WT rats began RG2833-treatment (cat #HY-16425, RG2833, MCE, Monmouth Junction, NJ) for 6 months, being sacrificed at 11 months of age.

Techniques: Transgenic Assay

Journal: Journal of Alzheimer's disease : JAD

Article Title: Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer’s disease rat model

doi: 10.1177/13872877251314777

Figure Lengend Snippet: RG2833 failed to improve spatial learning and memory deficits in TgF344-AD males. a, b Latency to first entrance during training trials, c latency to second entrance during test trial. d Representative track tracing of individual male performance for trial 6 across treatment conditions. a TGTR males perform as poorly as TGNT males during early acquisition (EA). b WTNT vs WTTR males perform similarly. c Male test data show no significant improvement in latency to second entrance following RG2833-treatment vs no drug-treatment. No differences were observed in the asymptomatic performance (AP, trials 4–6) across all comparisons (not shown). Repeated measure two-way ANOVA with Sidak’s post hoc tests were used in 3a and 3b. Ordinary two-way ANOVA with Sidak’s post hoc analysis was used in 3c ** P < 0.01. n = 12 WTNT, n = 8 TGNT, n = 13 TGTR, n = 16 WTTR. EA - Early Acquisition; AP – Asymptotic Performance; WTNT – Wild-type not treated; TGNT – transgenic not treated; WTTR – Wild-type RG2833-treated; TGTR – transgenic RG2833-treated; t – trial effect, d – drug effect. For simplicity, error bars are shown in one direction only.

Article Snippet: At 5 months of age TgF344-AD and WT rats began RG2833-treatment (cat #HY-16425, RG2833, MCE, Monmouth Junction, NJ) for 6 months, being sacrificed at 11 months of age.

Techniques: Transgenic Assay

Journal: Journal of Alzheimer's disease : JAD

Article Title: Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer’s disease rat model

doi: 10.1177/13872877251314777

Figure Lengend Snippet: Age and sex-dependent effects of RG2833 on WT and TgF344-AD rats. a - d Latency to first entrance during early acquisition (EA, trials 1 – 3). At 9-months of age, there is no significant drug effect on WT and TG rats independently of sex a - d . At 11-months of age, there is a drug positive effect on TG females a , and a negative effect on WT males d . WT males perform significantly better at 11-months than at 9-months of age d , but TG males do not b . No differences were observed in the asymptomatic performance (AP, trials 4–6) across all comparisons (not shown). Two-way ANOVA with Tukey’s post-hoc was used across two age points (9 and 11 months) and two drug-treatments (RG2833-treatment vs. no treatment). * P < 0.05, ** P < 0.01. Females n = 7 WTNT, n = 11 TGNT, n = 13 TGTR, n = 10 WTTR. Males n = 12 WTNT, n = 7 TGNT, n = 13 TGTR, n = 14 WTTR. EA - Early Acquisition; AP – Asymptotic Performance; WTNT – Wild-type not treated; TGNT – transgenic not treated; WTTR – Wild-type RG2833-treated; TGTR – transgenic RG2833-treated; age – age effect, d – drug effect. For simplicity, error bars are shown in one direction only.

Article Snippet: At 5 months of age TgF344-AD and WT rats began RG2833-treatment (cat #HY-16425, RG2833, MCE, Monmouth Junction, NJ) for 6 months, being sacrificed at 11 months of age.

Techniques: Transgenic Assay

Journal: bioRxiv

Article Title: Lysine deacetylation inhibition reverses TDP-43 mislocalization and in combination with arimoclomol ameliorates neuromuscular pathology

doi: 10.1101/2024.12.15.628528

Figure Lengend Snippet: Cytoplasmic (Cyt.) levels of TDP-43 ( A ) and TDP-35CTF ( B ) in control (Ctrl; n ≥ 6) and serum-deprived HEK293 cells (Starvation), untreated (Untr; n ≥ 6) or treated with 1 μM HDACi (n=3-6): SAHA, RGF109, RGFP966, ACY-738, tubastatin A (tubA) and selisistat. Dashed line indicates Ctrl level. ( C ) PPIAK125ac levels in total lysate of control (Ctrl; n=5) and serum-deprived HEK293 cells (Starvation), untreated (Untr; n=5) or treated with 1 μM SAHA (n=6). ( D ) PPIAK125ac levels in total lysate of HEK293 transiently transfected with siRNA control (Scramble; n=3), siRNA for HDAC1 (n=4) and HDAC3 (n=4). ( A-D ) Data (mean ± SEM) indicate WB immunoreactivity normalized to total protein loading ( A-D ) and to PPIA levels ( C-D ). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by one-way ANOVA, Dunnett’s multiple comparisons ( A-B ), Uncorrected Fisher’s LSD ( C ) or Tukey’s multiple comparisons ( D ) post-hoc tests.

Article Snippet: Drugs for cells and mice treatments were purchased from MedChemExpress and were as follows: SAHA (HY-10221), RGFP109 (HY-16425), RGFP966 (HY-13909); ACY-738 (HY-19327); tubastatin A (HY-13271A), selisistat (HY-15452), arimoclomol maleate (HY-106443A).

Techniques: Control, Transfection