Journal: Experimental & Molecular Medicine

Article Title: HMGCS2-dependent β-OHB/H3K9bhb ameliorates synaptic plasticity and cognition in Alzheimer’s disease

doi: 10.1038/s12276-026-01664-9

Figure Lengend Snippet: a , b , The representative immunoblots ( a ) and quantitative analyses ( b ) of Glun1, Glun2A, Glun2B and Syn1 in the hippocampus of the WT, 3xTg-AD and 3xTg-AD+β-OHB mice, n = 4 per group. c , RT–qPCR assays mRNA expression of the Glun1, Glun2A, Glun2B and Syn1 in the hippocampus of the WT, 3xTg-AD and 3xTg-AD+β-OHB mice, n = 5 per group. d , ChIP–qPCR analysis of the enrichment of H3K9bhb at Glun1, Glun2A, Glun2B, Glun2C and Syn1 promoters in the hippocampus of the WT, 3xTg-AD and 3xTg-AD+β-OHB mice, n = 5 per group. e , f , Supplementing with β-OHB could increase the density of 3xTg-AD dendritic spines detected by Golgi-cox staining; the representative images ( e ) and quantitative analysis ( f ) of spine, n = 5 per group, three fields per mice. Scale bar, 5 μm. g – j , The Sholl analysis showed the synaptic complexity of neurons after supplementing with β-OHB in 3xTg-AD mice; the representative images ( g and i ) and the quantitative analysis ( h and j ), n = 5 per group, two fields per mice. Scale bar, 50 μm. Data are shown as mean ± s.e.m. One-way ANOVA followed by Bonferroni’s post hoc test for b – d and f . Two-way ANOVA followed by Bonferroni’s post hoc test for i and k . * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: SYN1 , Synapsin-1 , Poly- , 1:1000 , Proteintech , 20258-1-AP.

Techniques: Western Blot, Quantitative RT-PCR, Expressing, ChIP-qPCR, Staining

Journal: Experimental & Molecular Medicine

Article Title: HMGCS2-dependent β-OHB/H3K9bhb ameliorates synaptic plasticity and cognition in Alzheimer’s disease

doi: 10.1038/s12276-026-01664-9

Figure Lengend Snippet: a – c , The HMGCS2 upregulation promotes the protein ( a and b ) and mRNA ( c ) expression of H3K9bhb, Glun1, Glun2A, Glun2B, Syn1 and PSD95, n = 4 or 5 per group. d , e , ChIP–qPCR analyses of the enrichment of H3K9bhb at Glun1, Glun2A, Glun2B and Syn1 promoters in the primary neurons of the WT, 3xTg-AD and 3xTg-AD + HMGCS2 mice n = 5 per group ( d ) and representative gel images from ChIP–qPCR assays ( e ). f – j , The HMGCS2 upregulation promotes the expression of Syn1 (scale bar, 25 μm) ( f ); n = 10 cells per group in MAP2 immunofluorescence ( g ) and quantitative analysis ( h ), n = 10 cells per group and SYP ( i and j ), n = 10 cells per group, scale bar, 15 μm. Data are shown as mean ± s.e.m. One-way ANOVA followed by Bonferroni’s post hoc test for b – d and j . Two-way ANOVA followed by Bonferroni’s post hoc test for h . * P < 0.05, ** P < 0.01 , *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: SYN1 , Synapsin-1 , Poly- , 1:1000 , Proteintech , 20258-1-AP.

Techniques: Expressing, ChIP-qPCR, Immunofluorescence

Journal: Experimental & Molecular Medicine

Article Title: HMGCS2-dependent β-OHB/H3K9bhb ameliorates synaptic plasticity and cognition in Alzheimer’s disease

doi: 10.1038/s12276-026-01664-9

Figure Lengend Snippet: a , b , A western blot analysis ( a ) of hippocampal lysates shows that HMGCS2 upregulation increases the protein levels ( b ) of H3K9bhb, Glun1, Glun2A, Glun2B, Syn1 and PSD95, n = 3 per group. c , The ChIP–qPCR analysis of H3K9bhb enrichment at the promoters of Glun2A , Glun2B , Syn1 and PSD95 in the four groups, n = 5 per group. d , The mRNA levels of Glun1, Glun2A, Glun2B, Syn1 and PSD95 in the hippocampus, as determined by RT–qPCR, n = 5 per group. e , f , Golgi staining reveals increased dendritic spine density in 3xTg-AD mice following overexpression of HMGCS2; representative images ( e ) and quantification ( f ) are shown, n = 5 per group, three fields per mice. Scale bar, 5 μm. g – j , A behavioral assessment of spatial learning and memory using the MWM, NOR and contextual fear conditioning tests: area under the curve (AUC) of escape latency during MWM training of day 1–6 ( g ), escape latency on day 7 of the MWM test ( h ), NOR discrimination index ( i ), freezing time on day 7 in the contextual fear conditioning test ( j ), n = 8 per group. Data are shown as mean ± s.e.m. One-way ANOVA followed by Bonferroni’s post hoc test for b – d , f and g – j . * P < 0.05, ** P < 0.01 , *** P < 0.001, **** P < 0.0001; ns, not significant.

Article Snippet: SYN1 , Synapsin-1 , Poly- , 1:1000 , Proteintech , 20258-1-AP.

Techniques: Western Blot, ChIP-qPCR, Quantitative RT-PCR, Staining, Over Expression

Journal: Science Advances

Article Title: Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons

doi: 10.1126/sciadv.adq6077

Figure Lengend Snippet: ( A ) Liquid phase–separated condensates formed after 1 hour at 37°C from 10 μM protein in Tyrode’s solution and without crowding agents. Scale bar, 1 μm. ( B ) Estimated size of protein condensates obtained from binary images [ n = 278, 151, 247, 280, and 268 aggregates for SYN1, SNCA, SNCA A53T mutant, Tau (TAU), and TDP-43, respectively]. Box plot with median and minimum/maximum whiskers. Kruskal-Wallis nonparametric test with Dunn’s correction for multiple comparison. ** P = 0.0064, *** P = 0.0002, and **** P < 0.0001. ( C ) Proportion of remaining condensates (left) and size of remaining condensates (right) after adding increasing concentrations of ATP ranging from 2 to 8 mM. Means ± SEM (pooled from four independent experiments). IC 50 , half-maximal inhibition concentration. ( D ) Representative images of SNCA (top) and SNCA A53T mutant (bottom) protein condensates and prefibrils after 1 to 3 hours of incubation at 37°C and after decondensation by 3.2 and 6.4 mM ATP, respectively. Scale bar, 5 μm. ( E ) Proportion of SNCA and SNCA A53T condensates (left; n = 202 and 244 condensates, respectively) and prefibrils (right; n = 4 and 11 prefibrils, respectively) after 3 hours of incubation at 37°C. Data collected and pooled from four independent experiments. Unpaired Student’s t test. ** P = 0.0038.

Article Snippet: Human recombinant full length protein SYN1 (#TP321273) was purchased from OriGene Technologies Inc. Human recombinant full-length proteins SNCA (#pro-393), SNCA A53T mutant (#pro-159), microtubule-associated protein Tau (#pro-295), ubiquitin ligase Parkin (PARK2, #pro-1840), APP N-terminal domain (#pro-1080), TAR DNA binding protein (TDP-43, #pro-2383), and RNA binding protein LIN28 (#pro-743) were purchased from ProSpec.

Techniques: Mutagenesis, Comparison, Inhibition, Concentration Assay, Incubation

Journal: Science Advances

Article Title: Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons

doi: 10.1126/sciadv.adq6077

Figure Lengend Snippet: ( A ) Representative images of liquid phase–separated SYN1 condensates formed in presence of 5% PEG and after 60′ without PEG at 37°C from 10 μM protein solutions under control condition (top) or after the addition of 8 mM ATP (bottom). Scale bar, 5 μm. ( B ) Distribution of SYN1 droplet sizes with and without PEG. Means ± SEM (pooled from four independent experiments), multiple unpaired Student’s t test. * P = 0.0061, 0.0326, 0.0482, and 0.0265. ( C ) Average size of SYN1 droplets with and without PEG. Means ± SEM (pooled from four independent experiments), unpaired Student’s t test. * P = 0.0258. ( D ) Normalized number of SYN1 droplets with and without PEG under control conditions or after the addition of ATP. Means ± SEM (pooled from four independent experiments), unpaired Student’s t test. ** P = 0.0049 and **** P < 0.0001. ( E ) Normalized size of SYN1 droplets with and without PEG under control conditions or after the addition of ATP. Means ± SEM (pooled from four independent experiments), unpaired Student’s t test. * P = 0.0182 and **** P < 0.0001.

Article Snippet: Human recombinant full length protein SYN1 (#TP321273) was purchased from OriGene Technologies Inc. Human recombinant full-length proteins SNCA (#pro-393), SNCA A53T mutant (#pro-159), microtubule-associated protein Tau (#pro-295), ubiquitin ligase Parkin (PARK2, #pro-1840), APP N-terminal domain (#pro-1080), TAR DNA binding protein (TDP-43, #pro-2383), and RNA binding protein LIN28 (#pro-743) were purchased from ProSpec.

Techniques: Control