Neuroprotective and neurorestorative properties of GDNF.
Glial cell line-derived neurotrophic factor (GDNF) promotes recovery of the injured nigrostriatal dopamine system and improves motor functions in both rodent and nonhuman primate models of Parkinson's disease (PD). The neurorestorative effects of a single administration of GDNF last for at least 1 month and can be maintained in rhesus monkeys by monthly injections. Adult midbrain dopamine neurons stimulated by GDNF show increased cell size, neurite extent, and expression of phenotypic markers. In parkinsonian nonhuman primates, GDNF treatment improves three of the cardinal features of PD: bradykinesia, rigidity, and postural instability. Although intracerebral administration is necessary because of the blood-brain barrier, intraventricular, intrastriatal, and intranigral routes of administration have been found to be efficacious in rodents and nonhuman primates. GDNF also induces neuroprotective changes in dopamine neurons which are active within hours after trophic factor administration. The powerful neuroprotective and neurorestorative properties of GDNF seen in preclinical studies suggest that trophic factors may play an important role in treating PD.
Gash
D M
DM
Department of Anatomy and Neurobiology and Center for Magnetic Resonance Imaging and Spectroscopy, University of Kentucky, College of Medicine, Lexington, USA.
Zhang
Z
Z
Gerhardt
G
G
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004298:Dopamine