title: A preclinical development strategy designed to optimize the use of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.
abstract: GDNF is a pleitropic neurotrophic factor which stimulates the dopaminergic phenotype in vitro and in vivo by way of activation of the GDNF/RET receptor complex. The pharmacologic profile of GDNF in two well-characterized animal models of Parkinson's disease suggests that the molecule may be useful in the treatment of neurodegenerative diseases involving dopaminergic dysfunction such as Parkinson's disease. This review summarizes the preclinical development path which was taken to develop GDNF as a novel therapeutic approach to treat Parkinson's disease based on GDNF's ability to regenerate dopamine neurons, including a description of the pharmacologic/biologic activities of GDNF. The overall aim will be to discuss these issues in the context of their potential therapeutic usefulness of GDNF to treat Parkinson's disease.
authors.forename: P A
authors.initials: PA
authors.lastname: Lapchak
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D009457:Neuroglia / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D013378:Substantia Nigra / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D002230:Carbidopa; D004298:Dopamine