GDNF Protein, Human (His)

Glial cell line-derived neurotrophic factor (GDNF) is a 134 amino acid protein belonging in the GDNF family ligands (GFLs). GDNF protein is widely distributed throughout both the central and peripheral nervous systems. Synthesis and secretion of GDNF occur in many cell types such as glial cells like astrocytes, oligodendrocytes, and Schwann cells; motor neurons (MNs); and skeletal muscle^[1].
Mature human GDNF shares 91-92% amino acid sequence identity with mouse, rat, and Canine GDNF proteins. While, mouse GDNF shares 99% aa sequence identity with rat GDNF protein.
GDNF is originally isolated from cultured B49 rat glial cells and found to enhance the survival and differentiation of dopaminergic neurons in primary cultures by promoting dopamine uptake. Similar to other members of the TGF-β superfamily, GDNF is first synthesized as a precursor protein (pro-GDNF). After a series of protein cleavage and processing, the 211 amino acid pro-GDNF is finally converted into the active and mature form of GDNF. GDNF has the ability to trigger receptor tyrosine kinase RET phosphorylation, whose downstream effects have been found to promote neuronal health and survival. The binding of GDNF to its receptors triggers several intracellular signaling pathways which play roles in promoting the development, survival, and maintenance of neuron-neuron and neuron-target tissue interactions. The synthesis and regulation of GDNF have been shown to be altered in many diseases, aging, exercise, and addiction. The neuroprotective effects of GDNF may be used to develop treatments and therapies to ameliorate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)^[1].
GDNF is a potent neurotrophic factor for regulating MN survival in the peripheral nervous system. GDNF prevents apoptosis of MNs during development in vivo, decreases the loss of MNs in animal models of motor neuropathy and degeneration, rescues MNs from axotomy-induced cell death, and protects MNs from chronic degeneration. Intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease^[1][2].

Recombinant human GDNF (100 ng/mL; 24 hours) increases transepithelial electric resistance (TER) significantly to 2.99 of baseline (2.23-fold of controls) in Caco2 cells. GDNF contributes to IEB maturation^[3].