Journal: Cell Communication and Signaling : CCS

Article Title: SENP5 enhances antiviral innate immunity by promoting AURKA-dependent STAT2 phosphorylation

doi: 10.1186/s12964-026-02808-0

Figure Lengend Snippet: SENP5 regulates JAK-STAT signaling and antiviral responses in an AURKA-dependent manner. A - C HEK293T cells were transfected with HA-tagged AURKA-WT, K258R or T288A mutant plasmid, followed by stimulation with IFN-α (1000 IU/mL) for 0.5 h ( A ), or 16 h ( B ), or VSV (MOI = 0.1, 12 h) ( C ). D A549 cells were transfected with AURKA-WT, K258R or T288A mutant plasmids or treated with a PP2A inhibitor Endothall (20 µM) as a control. The PP2A phosphatase activity was analyzed by a malachite green-based phosphate quantitation assay. E - F A549 cells were transfected with siRNA targeting AURKA in the presence or absence of Endothall treatment (20 µM), followed by stimulation with IFN-α (500 IU/mL) for 4 h ( E ), or 16 h ( F ). G - I HEK293T cells were transfected with Flag-SENP5 plasmid in the presence or absence of endogenous AURKA knockdown. The levels of p-STAT2 ( A , E , G ), VSV-G protein ( C , I ), and ISG15 mRNA ( B , F , H ) were measured by Western blotting and RT-qPCR, respectively. The data are presented as the mean ± SD of three independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001, ns: not significant

Article Snippet: Recombinant human interferon α-2a, AURKA inhibitor (Alisertib) and protein phosphatase 2 A (PP2A) inhibitor (Endothall) were purchased from MedChemExpress (New Jersey, USA).

Techniques: Transfection, Mutagenesis, Plasmid Preparation, Control, Activity Assay, Quantitation Assay, Knockdown, Western Blot, Quantitative RT-PCR

Journal: Cell Communication and Signaling : CCS

Article Title: SENP5 enhances antiviral innate immunity by promoting AURKA-dependent STAT2 phosphorylation

doi: 10.1186/s12964-026-02808-0

Figure Lengend Snippet: SENP5 promotes the JAK-STAT signaling and antiviral responses via deSUMOylation of AURKA. SENP5 is upregulated by virus infection, and regulates the deSUMOylation of AURKA. The deSUMOylation of AURKA reduced the activity of PP2A, relieving the AURKA-mediated suppression on STAT2 phosphorylation

Article Snippet: Recombinant human interferon α-2a, AURKA inhibitor (Alisertib) and protein phosphatase 2 A (PP2A) inhibitor (Endothall) were purchased from MedChemExpress (New Jersey, USA).

Techniques: Virus, Infection, Activity Assay, Phospho-proteomics

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: Alterations in PPP2R5C protein levels in NDEs from the plasma of AD patients (A) Representative TEM image of NDEs. Scale bars: 1 μm for low magnification and 100 nm for high magnification. (B) Nanoparticle tracking analysis of NDEs, confirming the expected size range. (C) Western blot analysis validation of NDEs and non-NDEs, using neuronal exosome markers, CD171 and synaptophysin; a microglia-derived exosome marker, Trem2; an astroglia-derived exosome marker, GLAST; and the exosome marker, Alix. (D) Label-free proteomic analysis of plasma NDEs showing differences in PPP2R5C protein levels among CN controls ( n = 4), pre-symptomatic familial AD mutation carriers (pre-FAD) ( n = 4), and familial AD (FAD) patients ( n = 5). (E) Targeted protein analysis comparing PPP2R5C protein levels in plasma NDEs across AD ( n = 20), aMCI ( n = 12), and CN groups ( n = 32). (F) Western blot analysis showed the difference in PPP2R5C levels in NDEs between AD, aMCI, and CN groups. All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗ p < 0.05 and ∗∗ p < 0.01 with Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Clinical Proteomics, Western Blot, Biomarker Discovery, Derivative Assay, Marker, Mutagenesis

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: Diagnostic utility of plasma PPP2R5C protein levels in AD (A) Plasma PPP2R5C protein levels in AD, aMCI, and CN groups by ELISA technology. AD, n = 74. aMCI, n = 76. CN, n = 74. (B) Evaluation of the diagnostic performance of plasma PPP2R5C protein levels in distinguishing AD from aMCI and CN. (C–F) Spearman correlation analysis between plasma PPP2R5C levels, Mini-Mental State Examination (MMSE) scores, and other AD biomarkers, including p-Tau T181, p-Tau S231, and p-Tau T217. (G) Representative western blots for PPP2R5C in brain tissues from young individuals, cognitively normal elderly individuals, and AD patients. (H) Quantitation of PPP2R5C levels, normalized to young CN ( n = 5 or 7). (I–K) Representative immunohistochemistry images of PPP2R5C (I), AT-8 (J), and p-Tau T181 (K) levels in the hippocampus of healthy controls and Braak-graded AD brain slices. Scale bars: 1 mm in (I, left), 50 μm in (I, right), and 1 mm in (J and K). (L) Quantitation of PPP2R5C, p-Tau T181, and AT8 levels (sample quantify, health ctr: 5, Braak II: 9, Braak III: 5, and Braak IV: 4). (M) Difference of plasma PPP2R5C protein levels among AD ( n = 34), PSP ( n = 28), and FTD ( n = 37) patients using ELISA. (N) ROC curve analysis assessing the discriminative power of plasma PPP2R5C protein levels for distinguishing AD from PSP and FTD. All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, and n.s., no statistics with one-way ANOVA with Tukey’s multiple comparisons test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Diagnostic Assay, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Western Blot, Quantitation Assay, Immunohistochemistry

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: PPP2R5C interacts with Tau and attenuates its expression (A) Co-immunoprecipitation analysis demonstrating the interaction between PPP2R5C and Tau protein. (B) Representative western blots immunostained for t-Tau, p-Tau T181, p-Tau S202, and p-Tau S396, in HEK293 cell lysates following PPP2R5C overexpression. (C) Quantification of t-Tau, p-Tau T181, p-Tau S202, and p-Tau S396, normalized to vector ( n = 6). (D) Representative western blots showing t-tau, p-Tau T181, p-Tau S202, and p-Tau S396 in primary neurons from Tau P301S mice following PPP2R5C overexpression. (E) Quantification of t-Tau, p-Tau T181, p-Tau S202, and p-Tau S396 levels, normalized to vector ( n = 6). (F and G) Double-labeling immunofluorescence analysis of GFP (green) and t-Tau/p-Tau T181 (red) was conducted on primary Tau P301S neurons after PPP2R5C overexpression. Scale bars, 10 μm. (H and I) Quantification of t-tau and p-Tau T181 fluorescence intensities ( n = 6). (J) Representative DiI staining shows the difference in spine density in tau P301S neurons after PPP2R5C overexpression. Scale bar: 10 μm. (K) Quantification of the density of spines ( n = 10). All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗∗ p < 0.01 and ∗∗∗ p < 0.001 with Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Expressing, Immunoprecipitation, Western Blot, Over Expression, Plasmid Preparation, Labeling, Immunofluorescence, Fluorescence, Staining

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: Overexpression of PPP2R5C in Tau P301S mice reduces AD-like pathogenesis and rescues cognitive function (A) Schematic representation of the experimental design. Two-month-old Tau P301S mice were injected with either AAV-hSyn-EGFP or AAV-hSyn-PPP2R5C-EGFP. Mice were sacrificed 6 months after AAV injection. (B and C) Morris water maze analysis as escape latency (s) and escape latency on day 4 (s). (D) Probe trial performance of Morris water maze test. (E) Swim speed of mice injected with AAVs encoding EGFP or PP2R5C-EGFP ( n = 8–10 mice per group). (F) Time spent in the novel arm in the Y-maze test ( n = 8–10 mice per group). (G, I, and K) Representative immunostaining images of t-Tau, p-Tau T181, and AT8 in the hippocampus of Tau P301S mice injected with AAVs encoding EGFP or PPP2R5C-EGFP. Scale bars: 200 μm for 4× images and 20 μm for magnified images. (H, J, and L) Quantification of immunoreactivity for t-Tau, p-Tau T181, and AT8 ( n = 5 mice per group). (M and N) Representative western blots showing Tau pathology in mouse brain tissue following PPP2R5C overexpression ( n = 6 mice per group). (O) Golgi staining revealed the dendritic spines in the apical dendritic layer of the CA1 region. Scale bar, 10 μm. (P) Quantification of spine density ( n = 6 mice per group). (Q) Representative electron microscopy of the synapse structures. Arrows indicate synapses. Scale bar, 1 μm. (R) Quantification of synaptic density ( n = 6 mice per group). All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, and n.s., no statistics, Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Over Expression, Injection, Immunostaining, Western Blot, Staining, Electron Microscopy

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: Knockdown of PPP2R5C in Tau P301S mice worsens cognitive dysfunctions (A) Schematic representation of the experimental design. Two-month-old Tau P301S mice were injected with either AAV-sh-Ctrl-EGFP or AAV-sh-PPP2R5C-EGFP. Mice were sacrificed 4 months after AAV injection. (B and C) Morris water maze analysis as escape latency (s) and escape latency on day 4 (s). (D) Probe trial performance of Morris water maze test. (E) Swim speed of mice injected with AAVs encoding sh-Ctrl-EGFP or sh-PPP2R5C-EGFP ( n = 8–10 mice per group). (F) Time spent in the novel arm in the Y-maze test ( n = 8–10 mice per group). (G, I, and K) Representative immunostaining images of t-Tau, p-Tau T181, and AT8 in the hippocampus of Tau P301S mice injected with AAVs encoding sh-Ctrl-EGFP or sh-PPP2R5C-EGFP. (H, J, and L) Quantifying immunoreactivity for t-Tau, p-Tau T181, and AT8 ( n = 4 mice per group). Scale bars: 200 μm for 4× images and 20 μm for magnified images. (M and N) Representative western blots showing Tau pathology in mouse brain tissue following PPP2R5C knockdown ( n = 6). (O) Golgi staining revealed the dendritic spines in the apical dendritic layer of the CA1 region. Scale bar, 10 μm. (P) Quantification of spine density ( n = 6 mice per group). (Q) Electron microscopy of synapses (left) and high magnification of synapses (right). Scale bar: 2 μm in the left panel, 200 μm in the right panel. (R) Quantification of synaptic density ( n = 6 mice per group). All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, and n.s., no statistics, Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Knockdown, Injection, Immunostaining, Western Blot, Staining, Electron Microscopy

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: PPP2R5C promotes Tau degradation and dephosphorylation by regulating autophagy and PP2A activity (A) Representative western blots show autophagy-lysosome inhibitors NH4Cl, Leu, and CQ prevent PPP2R5C-derived Tau degradation. (B) Quantifying relative Tau, p-Tau T181, p-Tau S202, and p-Tau S396 protein levels ( n = 6). (C) EM morphometric analysis of autophagic vacuoles in conditions of starvation combined with OA treatment and autophagic flux blockade combined with (PPP2R5C + LP) or without (PPP2R5C) treatment. Scale bar, 1 μm. (D) Representative IF images of AT8 and p62 after Tau P301S primary neurons infected with GFP-PPP2R5C/shPPP2R5C lentivirus. Scale bar, 10 μm. (E) Quantification of fluorescence density of p62 in neurons. ( n = 10). (F and H) Representative IF images of SH-SY5Y cells co-transfected with tandem mCherry-GFP-tagged autophagy marker LC3 plus empty vector or FLAG-PPP2R5C or siPPP2R5C. Autophagosomes were visualized with yellow dots (mCherry and GFP co-localization) and autolysosomes were identified as red dots (mCherry). Scale bars: 10 μm in normal and 2 μm in Enlargement. (G and I) Quantification of puncta ratio of yellow vs. red ( n = 10). (J) Enzymatic reaction kinetics of PP2A with different concentrations of pThr peptide. PP2A was isolated from HEK293 cells with the treatment of a PP2A inhibitor OA, FLAG-PPP2R5C, or siPPP2R5C ( n = 6). (K) Western blot confirms the changes in PPP2R5C levels. All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗∗ p < 0.01, ∗∗∗ p < 0.001, and n.s., no statistics, Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: De-Phosphorylation Assay, Activity Assay, Western Blot, Derivative Assay, Infection, Fluorescence, Transfection, Marker, Plasmid Preparation, Isolation

Journal: Cell Reports Medicine

Article Title: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

doi: 10.1016/j.xcrm.2026.102631

Figure Lengend Snippet: PPP2R5C triggers autophagy through ULK1-PPP2R5C direct binding activation (A) Western blot showing p -ULK1 Ser556 negatively correlated with PPP2R5C expression. (B) Binding positions and interaction mode analysis of proteins ULK1 and PPP2R5C. The binding interface was shown as a surface, and each protein was shown as a cartoon (right). The detailed molecular interactions of salt bridges, hydrogen bonds, and hydrophobic interactions were shown in the enlarged image, and residues on the protein interface are shown as sticks. (C) Co-immunoprecipitation assay to detect the interaction between PPP2R5C and ULK1 in HEK293 cells with FLAG-PPP2R5C or FLAG vector transfection. The co-precipitated ULK1 was subsequently detected by western blot analysis. (D) PPP2R5C and ULK1 interaction determined by co-immunoprecipitation and western blot in the cortex of WT and Tau P301S. (E) Immunofluorescence co-localization was used to observe the spatial location of PPP2R5C and ULK1 in the TauP301S and their WT littermates. Scale bars: 50 μm in normal and 20 μm in Enlargement. (F) Quantification of colocalization in (E) ( n = 5). (G) Mechanism diagram. In the early stages of AD, PPP2R5C protein levels begin to decrease. As a PP2A enzyme catalytic subunit B family member, PPP2R5C plays a role in AD pathology by influencing Tau protein phosphorylation. Additionally, the reduction of PPP2R5C affects the ULK1-PPP2R5C-autophagy pathway, resulting in elevated total Tau (t-Tau) protein levels, further contributing to AD progression. All the western blot data are representative of three independent experiments. Quantification data are expressed as mean ± SEM (∗∗ p < 0.01, Student’s t test).

Article Snippet: The Flag-PPP2R5C plasmid was modified from Flag/ZsGreen-PPP2R5C, siRNA PPP2R5C was purchased from Santa Cruz Biotechnology (#sc-45847).

Techniques: Binding Assay, Activation Assay, Western Blot, Expressing, Co-Immunoprecipitation Assay, Plasmid Preparation, Transfection, Immunoprecipitation, Immunofluorescence, Phospho-proteomics