Figure 9.

Proposed schema of the mechanisms by which LDN-193189 suppresses temperature-controlled repeated thermal stimulation (TRTS)-induced PC12 cell neuritogenesis. Hypothetically, treating PC12 cells with TRTS activates BMP receptor-mediated p38 MAPK signaling, which is essential for promoting the neuronal differentiation of PC12 cells. Thus, the inhibition of BMP type I receptor kinase activity with LDN-193189, a BMP signaling inhibitor, inhibits TRTS-mediated neuritogenesis in PC12 cells. This hypothesis also proposes an unknown crosstalk mechanism between the signaling pathways underlying BMP receptor- and NGF-mediated neuritogenesis. BMP, bone morphogenetic protein; BMPRI, BMP type I receptor; BMPRII, BMP type II receptor; ERK, extracellular signal-regulated kinase; NGF, nerve growth factor; TrkA, tropomyosin receptor kinase A.