Fig. 5: Hyaluronan fragmentation ameliorates LB-induced neurodegeneration by reducing toxic-α-syn load.

a Experimental timeline for (b–d). Hyaluronidase (Hyase) effect lasts only a few days post-injection, since HA is rapidly replenished in vivo. b TH staining shows partial neuroprotection in the ipsilateral SN 4 months after LB + Hyase inoculation. Scale bar, 200 µm. c, d Stereology revealed a reduction (from 40% to 20%) in dopaminergic cell loss when LB were co-injected with Hyase or low-molecular weight HA (LMW-HA), but not with chondroitinase ABC (ChABC), suggesting an effect mediated by HA breakdown. Graphs show TH-positive cell count (c) and ipsilateral/contralateral TH-positive cell ratio (d) (One-way ANOVA with Tukey’s post-hoc test, n = 4–6 mice). e Experimental timeline for (f–m). Animals were euthanized at the peak of Hyase effect. f Confocal micrographs and quantification of human α-syn staining in the SN 72 h after LB + Hyase injection show decreased exogenous α-syn load. Scale bar, 50 µm. Color bar represents fluorescence intensity. g Microglial cells surround a human α-syn-positive cell. Scale bar, 10 µm. h Substantial microglial activation in LB + Hyase-treated SN shortly after injection, suggesting an early effect of HA cleavage. Scale bar, 100 µm. i–l Quantification of Iba1-positive cells, Iba1, CD68 and HABP levels 72 h after LB inoculation co-injected with various ECM-modification molecules (two-way ANOVA with Holm–Sidak’s post-hoc test, n = 4 mice). m Fractal analysis of HABP staining confirms HA matrix disruption by Hyase (two-way ANOVA with Holm–Sidak’s post-hoc test, n = 4 mice). Data expressed as mean ± SEM. Source data are provided as a Source data file. See also Supplementary Figs. 7 and 8.