Evaluation of Glial Cell Line-Derived Neurotrophic Factors as Therapeutics: Pharmacogenomic and Pharmacoproteomic Studies

The glial cell line-derived neurotrophic factor (GDNF) family, which includes GDNF, artemin, persephin, and neurturin, rests within the transforming growth factor-beta superfamily. GDNF family members play a crucial role in the development of peripheral autonomic and sensory neurons. Recent studies on the impact of GDNF on posttraumatic nerve regeneration and the treatment of neuropathic pain found that GDNF reversed the posttraumatic changes. This paper focuses on different pharmacological effects of GDNFs that are currently under examination enabled by pharmacogenomic and pharmacoproteomic studies. From these lessons learned, it seems clear that GDNF is involved in the mechanism of action of drugs that improve neurodegenerative diseases and drug abuse, including alcohol. Although it is difficult to postulate precisely GDNF pathway-specific drugs at this time, identification of genes or proteins that are specifically regulated by GDNF in certain cellular phenotypes might improve the efficacy of neurodegenerative disease therapies. Additionally, the possibility of fine-tuning GDNF expression in specific brain sites suffering from neurotrophic factor malfunction might allow refinement of the personalized strategies used to fight neuronal disorders.