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. 2023 Apr 19;14:2150. doi: 10.1038/s41467-023-37464-2

Fig. 6. PDpep1.3 reduces endogenous a-syn levels and rescues lysosomal activity in human PD cell models.

Fig. 6

A Representative images of fibroblasts from a PD patient with SNCA triplication transduced with Scramble1.3-RFP or PDpep1.3-RFP (scale bars = 10 µm). B Quantification of relative a-syn fluorescence in RFP-positive fibroblasts. Bars represent means ± s.e.m. (one-way ANOVA, F(3, 36) = 6.159; P = 0.0017 followed by Dunnett’s post-test; n = 3). C Endolysosomal flux assay using confocal microscopy in SNCA triplication fibroblasts transduced with AAV-Scramble1.3-RFP or AAV-PDpep1.3-RFP. Cells were treated as indicated with Bafilomycin A1 (Baf). Bars represent means ± s.e.m. (nested one-way ANOVA, F(3, 10) =  = 23.70; P < 0.0001 followed by Dunnett’s post-test; n = 3). D Representative images of human iPSC-derived dopaminergic neurons with A53T a-syn mutation or isogenic controls without a-syn mutation. These iPSC-derived dopaminergic neurons were transduced with Scramble1.3-RFP or PDpep1.3-RFP and immunostained with anti-a-syn, anti-TH, or anti-LAMP1 antibodies (scale bars = 5 μm). E Quantification of relative a-syn fluorescence intensity in RFP-positive A53T mutant and control iPSC-derived dopaminergic neurons. Bars represent means ± s.e.m. (two-tailed nested t-tests; A53T, t(78) = 5.096, P < 0.001; Control, t(75) = 0.2708, P = 0.80; n = 3). F Quantification of relative LAMP1 fluorescence intensity in RFP-positive A53T mutant and control iPSC-derived dopaminergic neurons. Bars represent means ± s.e.m. (two-tailed nested t-tests; A53T, t(55) = 4.748, P = 0.009; Control, t(54) = 0.7178, P = 0.51; n = 3). G Representative images of human iPSC-derived dopaminergic neurons with A53T a-syn mutation or isogenic controls without a-syn mutation. These iPSC-derived dopaminergic neurons were transduced with Scramble1.3-RFP or PDpep1.3-RFP and immunostained with anti-a-syn oligomer or anti-TH antibodies. H Quantification of relative a-syn oligomer fluorescence intensity in RFP-positive A53T mutant and control iPSC-derived dopaminergic neurons. Bars represent means ± s.e.m. (nested one-way ANOVA, F(3, 115) = 4.715, P = 0.0039 followed by Dunnett’s post-test, n = 3).*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns indicates P > 0.05. Source data are provided as a Source Data file.