Extended Data Fig. 5: Impact of acute pharmacological inhibition of CMA on the synaptic proteome.
a, Timeline for treatment of whole-brain slices with the CMA inhibitor CIM7 (5 µM, 24 h) or vehicle (Veh.) and incubated with or without lysosomal protease inhibitors (20 mM ammonium chloride and 400 μM leupeptin, NL) for 20 h. b, Transcriptional CMA score (left) and heat map (right) of normalized expression (z-scoring) of CMA network genes (organized by the indicated functional groups) measured by qRT-PCR in female (triangles) and male (open circles) mice brains. c,d, Comparative proteomics analysis of proteins elevated by >1.5 folds in L2AKO and CIM7 treated brain slices relative to their respective controls (Ctrl) in females (c) and males (d). e, Representative immunoblot (top) and quantification (bottom) of lysosomal degradation of Synapsin-I in ex vivo whole-brain slices from WT mice upon NL incubation with CIM7 or vehicle as in a. The dotted lines in e indicate no changes relative to untreated samples (NL/untreated = 1). n = [4] (b),[6] (e) mice per group. Two-tailed paired Student’s t-test is used. Data are presented as mean values ±SEM.
