Parkinson’s disease (PD) is a movement disorder caused by the slow progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Modern medicine still cannot cure the disease or slow down its progression. Only symptomatic treatments are currently available.
Glial cell line-derived neurotrophic factor (GDNF) is a physiological neurotrophic factor that supports and regenerates DA neurons in the brain. Its clinical use is limited: the protein does not penetrated blood-brain barrier and hence must be administered directly into the brain. Orally active small molecular weight GDNF mimetics would overcome this limitation. GDNF and related proteins NRTN, ARTN and PSPN, called GDNF family ligands (GFLs), signal via receptor complex consisting of the signal-transmitting receptor tyrosine kinase RET shared by all four proteins and the ligand binding co-receptor GDNF family receptor alpha (GFRα) that provides binding specificity. The binding of a ligand to the receptor induces autophosphorylation of RET and triggers its downstream signaling cascadesthat control cell fate (Airaksinen & Saarma, 2002).
GDNF mimetics is a collaborative project, which was launched in 2013 between Molcode Ltd. and University of Helsinki. Our main goal is to study and develop ‘GDNF mimetics’ to potentially find disease-modifying treatment against PD.
As a starting point of this project we had a set of chemical compounds, able to activate GDNF receptors and intracellular signaling.