Journal: Molecular Neurodegeneration
Article Title: Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer’s disease through disrupted regulated intramembrane proteolysis
doi: 10.1186/s13024-025-00864-7
Figure Lengend Snippet: JAK-STAT signalling pathways are disrupted in PSEN1 mutant astrocytes. ( A-B ) FACs analysis of cell surface levels of IFNAR2 in CD44-positive iPSC-astrocytes, with and without TIC treatment. Data represent 5 experimental repeats from two batches and include 2 control lines and 2 PSEN1 mutant lines. Note that two control lines are pooled for TIC-treated datapoint. Data analysed within treatment subgroups via one-way ANOVA. ( C ) Representative Western blot of iPSC-astrocyte lysates with or without TIC treatment for 24 h. Actin is shown as a loading control. ( D-G ) Western blot analysis of total and phosphorylated MAPK (p42/p44), STAT2, STAT3 and NFκB under basal conditions or after 24 h TIC treatment. Note that one outlier was removed (grey arrow in panel A), due to a z score of 3.47. Data represent up to 4 independent batches and up to 7 technical repeats using 5 controls and 3 PSEN1 mutant lines (see Table ). For data separated by iPSC line, see Fig . ( H-J ) qPCR analysis of ISG15 , OAS1 and CXCL10 ; genes involved in interferon response (associated with JAK-STAT2 signalling). Note that CXCL10 was rarely detectable in untreated conditions (n.d.). Data represent up to 5 independent batches and up to 6 technical repeats from 6 control lines and 3 PSEN1 lines, see Table . For data separated by iPSC line, see Fig . ( K ) High content imaging analysis of nuclear NFκB normalised to cytosolic NFκB and plotted as a fold-change relative to maximum signal. Data represent 2 control lines and 3 PSEN1 lines, with two experimental repeats (see Table ). Individual data presented in Fig . Pairwise comparisons represent two tailed t-tests, where * = p < 0.05, ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001
Article Snippet: IFNAR2-APC , human , Miltenyi Biotec 130-099-560 , RRID: AB_2652223.
Techniques: Mutagenesis, Control, Western Blot, Imaging, Two Tailed Test
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