Fig. 4: PDpep1.3 reduces a-syn-mediated neurodegeneration in C. elegans and an a-syn oligomer rat model. | Nature Communications

Fig. 4: PDpep1.3 reduces a-syn-mediated neurodegeneration in C. elegans and an a-syn oligomer rat model.

From: Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease

Fig. 4: PDpep1.3 reduces a-syn-mediated neurodegeneration in C. elegans and an a-syn oligomer rat model.

A Representative image of an adult C. elegans with PDE neuron visualized using dat-1p::gfp(egIs1) (scale bar = 20 μm) (top panel). Neurite length for each PDE neuron was categorized as: Short (does not extend past the vulva; purple), Medium (extends past the vulva but not beyond halfway to ADE neuron; cyan), or Long (extends to ADE neuron; yellow) (created using an image from somersault1824 at https://somersault1824.gumroad.com/). B Frequencies of PDE neurite lengths were compared for C. elegans expressing no a-syn versus a-syn alone (Pearson Chi-Square test, χ2(2, 1252) = 169.0; P < 0.0001), a-syn with RFP (a-syn;TagRFP Marker+) versus a-syn without RFP (a-syn;TagRFP Marker-) (Pearson Chi-Square test, χ2(2, 910) = 1.332; P = 0.5137), and a-syn with RFP-PDpep1.3 (a-syn;TagRFP::PDpep1.3 Marker+) versus a-syn without RFP-PDpep1.3 (a-syn;TagRFP::PDpep1.3 Marker-) (Pearson Chi-Square test, χ2(2, 1528) =  86.1729; P < 0.0001). C Representative images of native YFP and RFP fluorescence and immunostaining with anti-tyrosine hydroxylase (TH) antibody in substantia nigra (SN) of rats injected with V1S/SV2 or YFP plus Scramble1.3-RFP or PDpep1.3-RFP (scale bars = 200 μm). Quantification of YFP+ area in SN of rats injected with D V1S/SV2 (unpaired two-tailed t-test, t(16) = 2.317; P = 0.0341; Scramble1.3, n = 8 rats; PDpep1.3, n = 10 rats) or E full-length YFP (unpaired two-tailed t-test, t(15) = 1.003; P = 0.3317; Scramble1.3, n = 8 rats; PDpep1.3, n = 9 rats). Quantification of YFP+ area in striatum of rats injected with F V1S/SV2 (unpaired two-tailed t-test, t(16) = 2.193; P = 0.0434; Scramble1.3, n = 8 rats; PDpep1.3, n = 10 rats) or G full-length YFP (unpaired two-tailed t-test, t(13) = 1.140; P = 0.2749; Scramble1.3, n = 6 rats; PDpep1.3, n = 9 rats). H Quantification of a-syn+ area in SN (unpaired two-tailed t-test, t(16) = 2.843; P = 0.0118; Scramble1.3, n = 8 rats; PDpep1.3, n = 10 rats), I TH+ cell counts in SN (unpaired two-tailed t-test, t(15) = 2.421; P = 0.0286; Scramble1.3, n = 8 rats; PDpep1.3, n = 9 rats), and J TH fluorescence in striatum (unpaired two-tailed t-test, t(16) = 2.664; P = 0.0170; Scramble1.3, n = 8 rats; PDpep1.3, n = 10 rats) at 6 weeks post-injection of V1S/SV2 plus Scramble1.3-RFP or PDpep1.3-RFP. Bars represent means ± s.e.m. *P < 0.05; ****P < 0.0001; ns indicates P > 0.05. Source data are provided as a Source Data file.

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