GDNF is a glycosylated, disulfide-bonded homodimer molecule. It was first discovered as a potent survival factor for midbrain dopaminergic neurons and was then shown to rescue these neurons in animal models of Parkinson's disease. GDNF is about 100 times more efficient survival factor for spinal motor neurons than the neurotrophins. FUNCTION: Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. SUBUNIT: Homodimer; disulfide-linked. SUBCELLULAR LOCATION: Secreted protein. ALTERNATIVE PRODUCTS: 2 named isoforms produced by alternative splicing. DISEASE: Defects in GDNF may be a cause of Hirschsprung disease (HSCR). In association with mutations of RET gene, defects in GDNF may be involved in Hirschsprung disease. This genetic disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction. DISEASE: Defects in GDNF are a cause of congenital central hypoventilation syndrome (CCHS); also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.