Fig. 9: HTRA1 treatment renders α-Syn non-toxic and seeding incompetent in primary mouse neurons. | Nature Communications

Fig. 9: HTRA1 treatment renders α-Syn non-toxic and seeding incompetent in primary mouse neurons.

From: HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species

Fig. 9: HTRA1 treatment renders α-Syn non-toxic and seeding incompetent in primary mouse neurons.

a Schematic showing experimental design. b Fibrillization of α-syn (100 μM) was conducted by shaking for 48 h at 37 °C in the presence of HTRA1, HTRA1S328A, HTRA2, buffer, or Aldolase (20 μM). Reaction products were applied to mouse primary hippocampal neurons at DIV 18–21. 24 h following treatment, cell viability was assessed by MTT assay. Each value is compared directly to α-syn + no treatment control using a series of two-sided Welch’s t-tests (N = 3 for α-syn monomer and HTRA2; N = 6 for aldolase; N = 7 for buffer, α-syn PFFs + buffer, HTRA1, and HTRA1-SA; N = 8 for no treatment, biological replicates are shown as dots, bars represent means ± SEM, *p = 0.031, **p = 0.0097). c Immunocytochemistry of neurons as treated in part b, 1 week following addition of α-syn/HTRA reactions. Endogenous phosphorylated-α-syn (green), tau (red), DAPI (blue). Scale bar, 20 μm.

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