Glial cell line-derived neurotrophic factor (GDNF) is a disulfide-bonded homodimeric protein. GDNF and its related factors neurturin (NRTN), persephin (PSPN), and artemin (ARTN) are being referred to as GDNF family ligands (GFLs) which belong to the TGF-β superfamily. They activate intracellular signaling cascades through a multicomponent receptor system, composed of the receptor tyrosine kinase RET and one of the four GFRα (α1-α4) receptors. GDNF is expressed by a number of cell types including type 1 astrocytes, Schwann cells, neurons, pinealocytes, and skeletal muscle cells. GDNF has been shown to promote the survival of various neuronal subpopulations in the central nervous system, including midbrain dopamine neurons and motoneurons. Furthermore it supports the survival and regulates the differentiation of many peripheral neurons, such as sympathetic, parasympathetic, sensory and enteric neurons. Outside the nervous system GDNF functions as a morphogen in kidney development and regulates spermatogonial differentiation.
