Glial cell line-derived neurotrophic factor: a novel therapeutic approach to treat motor dysfunction in Parkinson's disease.
The discovery of the novel neurotrophic factor glial cell-line derived neurotrophic factor (GDNF) in 1993 sparked the interest of basic neuroscientists and clinicians alike. Since that time, many aspects of GDNF's physiology and pharmacology have been studied in great detail. GDNF has been shown to be a potent survival factor for dopaminergic neurons during development. GDNF also has been shown to be a survival factor and neurotrophic factor for nigrostriatal dopaminergic neurons in the adult. The factor also reverses behavioral deficits in a rodent and primate model of Parkinson's disease. The overall goal will be to discuss the pharmacology of GDNF in the context of a potential therapeutic use to treat Parkinson's disease. Thus, the following report presents a comprehensive review of the development of GDNF's pharmacology and evidence which supports the clinical use of GDNF to treat dopaminergic deficits and motor dysfunctions in Parkinson's disease.
Lapchak
P A
PA
Department of Neuroscience MC-5-1-C, AMGEN Inc., Thousand Oaks, California 91320, USA.
Gash
D M
DM
Jiao
S
S
Miller
P J
PJ
Hilt
D
D
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000150:complications*
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004298:Dopamine