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[Preprint]. 2025 Apr 28:2024.04.18.590103. Originally published 2024 Apr 21. [Version 3] doi: 10.1101/2024.04.18.590103

Fig. 6. PP alleviates proteinopathies in preclinical models.

Fig. 6.

(a-e) RNA-seq was performed in the retina of 1 and 3 months-old wild-type and Rho P23H/+ mice. GO of differentially expressed genes (DEG) (FDR<0.1) (a, c) and GSEA comparing these DEG with that of PP (b, d). Heatmap of selective genes (e). (f-j) Retina explants isolated either from RhoP23H/+ mice P15 and cultured with PP or DMSO vehicle control or from wild-type mice cultured for 10 days ex vivo. (f) The morphology retinae were imaged and scanned before (Day 0) and after treatment (Day 10) by a webcam (top) and visible light optical coherence tomography (vis-OCT) with tissue thickness shown as a heatmap with a color legend indicating thickness from 0–300 µm (bottom). Scale, 1 mm. (g) and (h) are bar plots of retinal thickness and volume, respectively, measured from the vis-OCT scanning data. n=4~5 biologically independent samples. (i) Representative retinal histology images of the retina explants cultured for 10 days with black bars showing the outer nuclear layer (ONL). (j) The nuclei count in the outer nuclei layer (ONL) along six horizontal positions at peripheral-central-peripheral positions across each cross-section in (i). n=3–4 biologically independent samples. Similar results were confirmed in at least three independent experiments. (k-n) Male C155>UAS-hTau1.13 and C155 flies were fed with either standard diet or diet supplemented with 25µM PP. Quantification of distance travelled from larval crawling assay (n=10 biologically independent samples) (k), climbing index score from adult fly climbing assay at 14 days and 21 days (n=5 biologically independent cohorts/group) (l) of age, and lifespan assay (m) (n=32 flies for C155-Ctrl, n=65 flies for hTau-Ctrl and n=44 flies for hTau-PP). (n) Western blot and quantification of p-Tau (AT8 antibody) and total Tau (DAKO antibody) level in 21 days C155>UAS-hTau1.13 flies fed with control or PP diet (n=4 biologically independent samples). All data mean ± S.E.M. Statistical tests used: two-way ANOVA and Tukey multiple comparison for g and h, two-way ANOVA for j, unpaired two-tailed Studenťs t-test for k, l (day 21) and n. Log-rank (Mantel-Cox) test for m. The Western blot raw blot images are provided in the source data file.