Isoforms of glial cell line-derived neurotrophic factor and their therapeutic potential

Glial cell-derived neurotrophic factor (<i>GDNF</i>), first purified from glial cell culture medium, immediately attracted the interest of researchers due to its ability to enhance survival of midbrain dopaminergic neurons. This property suggested its therapeutic potential for Parkinson's disease as a socially significant disease. Numerous academic and preclinical studies in animal models supported this hypothesis, but clinical trials yielded conflicting results. For this reason, <i>GDNF</i> is not currently used clinically. However, robust and perspective results in experiments justify further research and overcoming the causes of absent therapeutic effect. Research of <i>GDNF</i> gene alternative splicing products has emerged as a promising avenue. Several <i>GDNF</i> isoforms exhibit effects similar to those of <i>GDNF</i> and differ by smaller size and less dose-response relationship. This makes small <i>GDNF</i> isoforms potentially successful as therapeutic components for some CNS diseases.