A potent neurotrophic factor that enhances survival of midbrain dopami
nergic neurons was purified and cloned. Glial cell line-derived neurot
rophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer tha
t is a distantly related member of the transforming growth factor-beta
superfamily. In embryonic midbrain cultures, recombinant human GDNF p
romoted the survival and morphological differentiation of dopaminergic
neurons and increased their high-affinity dopamine uptake. These effe
cts were relatively specific; GDNF did not increase total neuron or as
trocyte numbers nor did it increase transmitter uptake by gamma-aminob
utyric-containing and serotonergic neurons. GDNF may have utility in t
he treatment of Parkinson's disease, which is marked by progressive de
generation of midbrain dopaminergic neurons.