ASSESSING THE ABILITY OF GDNF MIMETICS TO MITIGATE THE PROGRESSION OF PARKINSON'S DISEASE BY INHIBITING NEUROINFLAMMATION

Increasing scientific data indicate the role of neuroinflammation in the pathology of Parkinson’s disease (PD). For now, PD is not curable. One of the therapeutically potent approaches to combat PD is neurotrophic factors (NTFs)-based therapies, particularly the glial cell line-derived neurotrophic factor (GDNF). Well-known effects of GDNF are related to supporting the survival and functioning of various neuronal populations in the body. However, this protein seems to also play less well-documented roles in glial cells, thus, influencing neuroinflammation. Here we aimed to evaluate the effects of small molecules targeting GDNF family ligands (GFLs) receptors on the expression of the satellite glial marker IBA1 in dorsal root ganglia of rats with surgery- and diabetes-induced neuropathy. Our data demonstrate the activation of GFLs receptors with either GFLs or small molecule agonists downregulated the expression of IBA1 in this tissue of experimental animals. While it can be a secondary effect due to a supportive role of GFLs in neuronal cells, growing body of evidence indicates that GFL receptors are expressed in glial and peripheral immune system cells. Thus, targeting GFL receptors with either proteins or small molecules may directly suppress the activation of glial and immune system cells and, therefore, reduce neuroinflammation. As neuroinflammation is considered to be an important contributor to the process of neurodegeneration these data further support research efforts to modulate the activity of GFL receptors in order to develop disease-modifying treatments for neurodegenerative disorders and neuropathic pain that target both neuronal and glial cells.