The Twofold Role of Osteogenic Small Molecules in Parkinson’s Disease Therapeutics: Crosstalk of Osteogenesis and Neurogenesis

Figure 1

Schematic representation of crosstalk between dopaminergic neurons and osteoblasts induced by small molecules involved in the Smurf1 signaling pathway is shown. (a) This picture highlights the effect of Smurf1 mimicking small molecules in neurogenesis. Induction of p-Smurf1 led to RhoA ubiquitination and resulted in less ubiquitinated Par6 in a competitive manner. This cascade along with cdc42 and Rac1-induced neurite outgrowth. However, RhoA, through the activation of Rho-associated protein kinases (ROCKs), phosphorylates myosin light chain (MLC) and LIMK, both of which separately phosphorylate cofilin. p-cofilin depolymerized actin and inhibited neuriotogenesis. In addition, GDNF, through an increase in Six2, degrades the P53 protein and induces Bcl2 overexpression, which leads to cell viability improvement. (b) This picture highlights the effect of Smurf1 mimicking small molecules in the inhibition of osteogenesis. Induction of Smurf1 and subsequent Smurf1 phosphorylation led to Runx2 degradation and osteogenesis inhibition.