Neuronal Hrs depletion accelerates synaptic protein loss and the accumulation of phosphorylated GluA1 receptors. A–D, Representative Western blottings and quantification of synaptic proteins in brain lysates of age-matched uninfected and prion-infected Hrs^f/fSyn1-Cre⁻ and Cre⁺ mice at terminal disease (A, B) or at 107 dpi (C, D; n = 3–8 mice/group). E, F, Representative Western blottings show phosphorylated GluA1 receptors (S831 and S845) relative to total protein levels (n = 3–4 mice/group). Data shown as mean ± SEM. Relative protein levels were normalized to the average of the uninfected Hrs^f/fSyn1-Cre mice. Two-way ANOVA with Tukey's multiple comparisons post hoc test (A, B and E, F), unpaired, two-tailed Student's t test (C, D). *p < 0.05, **p < 0.01, ***p < 0.001. Data supported by Extended Data Figures 6-1, 6-2, and 6-3.