Fig 2: Molecular simulations for the interaction between CD36 and UCHL1.a Three-dimensional crystal structure of CD36–UCHL1 complex. b Surface presentation of the CD36–UCHL1 complex crystal structure at 0 and 50 ns. c Plots of root mean square deviation (RMSD) of Calpha atom (RMSDCa, blue), RMSD of backbone (RMSDBb, red), and RMSD of all-heavy atom (RMSDAll, green).

Fig 3: The appearance of thalamic WFA+ puncta moderately associates with UCHL1+ neurons 7 days post-CCI. Representative images of the ipsilateral thalamus at 1 day post-CCI show normal expression of WFA (A), Iba1 (B), GFAP (C), and merged image (D). Representative images of the ipsilateral thalamus at 7 days after the sham procedure show normal expression of WFA (E), Iba1 (F), GFAP (G), and merged images (H). The appearance of ipsilateral thalamic WFA+ puncta (I,O,T) occurred in association with astrogliosis (GFAP, J; merged image K,L; quantified in M and N), microgliosis (Iba1, P; merged image Q,R; quantified in S), and UCHL1+ neurons (U; merged image V,W; quantified in X). High magnification image shows that GFAP (L), Iba1 (R), and UCHL1 (W) weakly colocalized with WFA+ puncta in the thalamus (white arrow demarcates WFA+ puncta). One-way ANOVA Dunnett’s post hoc test (M,N,S,X). Values represent means ± SD (n = 4, **P < 0.01; ***P < 0.001). Scale bars = 200 µm (A–K,O–Q,T–V) and 20 µm (L,R,W). WFA, wisteria floribunda agglutinin; UCHL1, ubiquitin C-terminal hydrolase L1; MFI, mean fluorescent intensity; CCI, controlled cortical impact; GFAP, Glial fibrillary acidic protein.

Fig 4: Upregulation of myocardial Uchl1 in post-MI mice occurs primarily in cardiomyocytes. Myh6-Cre transgenic (CTL) mice and mice with cardiomyocyte-restricted knockout of Uchl1 (CKO) at 10 weeks of age were subjected to sham surgery (Sham) or permanent LAD ligation (MI). For protein analyses, ventricular myocardium was sampled from the infarct and boarder (I + B) zone (A,B) or the remote area (C,D) of the post-MI mice or the equivalent areas of the sham control mice 7 days (7d) after LAD ligation. (A,C) Representative images of Western blot analyses for Uchl1 in the peri-infarct area (Peri-IF, A) and the remote zone (C). L.C., loading control, which used the images from staining-free gel imaging technology. (B,D) Scatter plots superimposed by mean ± SEM to show the pooled densitometry data from four mice (two males and two females) per group. The p-value of the pair-wise comparison is shown above the bracket and is derived from two-way ANOVA followed by Tukey’s test.

Fig 5: Effects of UCHL1 on the expression of mTOR, ERK, AMPK and GSK-3ß in cortical neurons after 1-hr OGD/24-hr R. Representative results of (A, C, E and G) and quantitative analysis (B, D, F and H) of Western blot showed the effects of UCHL1 shRNA treatments on the phosphorylation levels of mTOR, ERK, AMPK, GSK-3ß from Normoxia and OGD groups of cPKC?+/+ and cPKC?-/- cortical neurons (n = 6 per group), respectively. ***P < 0.001, **P < 0.01 versus Normoxia of cPKC?+/+ neurons; ### P < 0.001, ## P < 0.01 versus corresponding cPKC?+/+ cortical neurons with the same treatment; +++ P < 0.001 versus NC with the same treatment.