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.
MeSH terms
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Amino Acid Sequence
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Base Sequence
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Cell Differentiation / drug effects
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Cell Line
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Cell Survival / drug effects
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Cells, Cultured
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Cloning, Molecular
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Dopamine / biosynthesis*
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Glial Cell Line-Derived Neurotrophic Factor
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Humans
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Mesencephalon / cytology
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Mesencephalon / drug effects*
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Mesencephalon / metabolism
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Molecular Sequence Data
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Molecular Weight
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Nerve Growth Factors*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / isolation & purification
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Nerve Tissue Proteins / pharmacology*
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Neuroglia / metabolism*
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Parkinson Disease / drug therapy
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Rats
Substances
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GDNF protein, human
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Gdnf protein, rat
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Glial Cell Line-Derived Neurotrophic Factor
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Nerve Growth Factors
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Nerve Tissue Proteins
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Dopamine
Associated data
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GENBANK/L15305
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GENBANK/L15306