Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: comparison with GDNF and persephin.
Neurturin and persephin are recently discovered homologs of glial cell line-derived neurotrophic factor (GDNF). Here, we report that neurturin, like GDNF, increases the choline acetyltransferase activity of normal postnatal motor neurons, induces neurite outgrowth in spinal cord, and potently protects motor neurons from chronic glutamate-mediated degeneration. Persephin, in contrast, does not appear to have neurotrophic or neurite-promoting effects on mature motor neurons and may instead worsen the glutamate injury of motor neurons. This pattern in the TGF-beta family suggests certain receptor specificities, requiring at least the Ret/GFRalpha-1 receptor complex. The results predict potential benefit of neurturin, but not persephin, in the treatment of motor neuron disorders and spinal cord diseases.
Bilak
M M
MM
Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, Maryland, 21287-7519, USA.
Shifrin
D A
DA
Corse
A M
AM
Bilak
S R
SR
Kuncl
R W
RW
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid / Q000633:toxicity; D009046:Motor Neurons / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051101:Neurturin; D051381:Rats; D013116:Spinal Cord / Q000166:cytology
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D051101:Neurturin; C495057:Nrtn protein, rat; C110758:persephin; D018698:Glutamic Acid; D002795:Choline O-Acetyltransferase