Glial Cell Line-Derived Neurotrophic Factor Pathway (GDNF Pathway)

The glial cell line–derived neurotrophic factor (GDNF) pathway is a critical signaling system involved in the survival, development, and function of various neuronal populations. GDNF is a small, highly conserved protein that belongs to the transforming growth factor-β (TGF-β) superfamily and exerts potent neuroprotective effects. It is widely distributed throughout both the central and peripheral nervous systems and can be secreted by astrocytes, oligodendrocytes, Schwann cells, motor neurons, and skeletal muscle. The pathway involves the ligand GDNF, the co-receptor GFRα1, and the tyrosine kinase receptor RET. Activation of RET triggers downstream signaling cascades essential for neuronal survival and differentiation. Dysregulation of the GDNF pathway is implicated in various diseases, including Parkinson's disease, Hirschsprung's disease, neuropathic pain, liver fibrosis and some cancers, making it a target for therapeutic intervention.

Other names

GDNF signaling pathwayGDNF-GFRα-RET pathway

GDNF binds to GFRα1, leading to RET receptor activation and downstream signaling cascades including MAPK/ERK.