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      GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.

      Science (New York, N.Y.)

      cytology, Animals, Astrocytes, drug effects, Base Sequence, Cell Differentiation, Cell Line, Cell Survival, Cells, Cultured, Cloning, Molecular, Dopamine, biosynthesis, Glial Cell Line-Derived Neurotrophic Factor, Humans, Mesencephalon, Amino Acid Sequence, metabolism, Molecular Sequence Data, Molecular Weight, Nerve Growth Factors, Nerve Tissue Proteins, chemistry, genetics, isolation & purification, pharmacology, Neuroglia, Neurons, Parkinson Disease, drug therapy, Rats

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          Abstract

          A potent neurotrophic factor that enhances survival of midbrain dopaminergic neurons was purified and cloned. Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake. These effects were relatively specific; GDNF did not increase total neuron or astrocyte numbers nor did it increase transmitter uptake by gamma-aminobutyric-containing and serotonergic neurons. GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons.

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          8493557

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