Figure 7. TRIM11 mitigates α-Syn pathology, neurodegeneration, and behavioral defects in a PD mouse model.

(A) Schematic representation of stereotaxic injections (top) and experimental timeline (bottom).

(B) Representative immunofluorescence images of pSyn and TRIM11-HA/GFP in frontal cortex and piriform cortex of AAV9-GFP- and AAV9-TRIM11-injected mice. Scale bar, 100 μm.

(C and D) Representative IHC images of pSyn in cortical regions (C) and percentage of the total area occupied by pSyn inclusions (D; mean + SD, n ≥ 4 mice).

(E and F) Representative IHC images of TH-positive neurons in the injected ipsilateral and the non-injected contralateral regions (Scale bar, 190 μm) (E) and quantification of TH-positive neuron loss relative to the contralateral side of the same brain (mean + SEM, n ≥ 4 mice) (F).

(G) Distance travelled in each quadrant by AAV9-GFP and AAV9-TRIM11 mice during the open-field test. Data are the mean ± SEM (n ≥ 11 mice).

(H and I) Total distance travelled by (H), and total freezing time of (I), AAV9-GFP and AAV9-TRIM11 mice during the open-field test (mean ± SEM, n ≥ 11 mice).

(J) A model for the multiple roles of TRIMs in protein quality control. TRIMs prevent protein misfolding (a) and amorphous and fibrillar aggregation (b). They also dissolve pre-existing aggregates (b’) and promote their refolding (a’). For defective or terminally misfolded proteins, TRIMs may mark them with poly-SUMO2/3 chains (c), enabling them to be ubiquitinated by STUbLs (d) and subsequently degraded in the proteasome (e).

*P < 0.05, **P < 0.01.