Figure 9.

Activation of p-ASK1, p-JNK, and p-p38 pathways in SNc neurons of sporadic PD patients. A–E, p-ASK1 staining in the SNc neurons of human brains. The SNc neurons of PD patients exhibited increased staining for p-ASK1 compared with control subjects (A). In PD patients, the most common staining pattern of p-ASK1 was a granular, cytoplasmic distribution (B, arrowheads). In 33% of cases, p-ASK1 staining was colocalized with Lewy body/pale body staining (C, arrow). In normal control subjects and in disease specificity controls with pure Alzheimer's disease, a few neurons exhibiting p-ASK1 immunoreactivity typically showed a light diffuse staining pattern (D, right cell), and 99.4% of neurons were negative (D, left cell). Double-label immunofluorescence confirmed colocalization of α-synuclein (red) with p-ASK1 (green) in the Lewy body (arrow), on a background of granular cytoplasmic p-ASK1 staining (E, arrowheads). F–H, p-p38 and p-JNK staining in the SNc neurons of human brains. Significantly more SNc neurons from PD patients exhibited immunoreactivity for p-p38 and for p-JNK (F). While p-p38 and p-JNK staining was not colocalized with α-synuclein, >70% of neurons with granular p-p38 (G, green) or p-JNK (H, green) staining also showed abnormal α-synuclein aggregation (red). The outline of the individual neuron is indicated by dashes. Scale bars: B–D, 25 μm; E–H, 10 μm. *p < 0.05 versus control.