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Glial-Derived Neurotrophic Factor (GDNF) is a member of the TGF-β superfamily. GDNF signals through a multi-component receptor system, composed of a RET protooncogene and one of the four α1-α4 receptors1.
GDNF promotes survival of various neuronal cells, including motoneurons2,3, Purkinje cells and sympathetic neurons4. In embryonic midbrain cultures, GDNF promotes the survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake5. Cells that express GDNF include Sertoli cells, type 1 astrocytes, Schwann cells6, neurons, pinealocytes, and skeletal muscle cells7.
In vivo, following transection of facial motor neuron axons, locally applied GDNF has been shown to rescue virtually all damaged neurons from death8. GDNF may be of clinical relevance in the treatment of Parkinson's disease that is characterized by progressive degeneration of midbrain dopaminergic neurons9,10.
Recently, it has been hypothesized that functional, carboxy-terminally amidated peptides are processed from the GDNF precursor upon proteolytic cleavage by furin-like endopeptidase11,12,13. Those different peptides (a 5-mer and 11-mer) have not been isolated endogenously to date. However, the rat 11-mer sequence (named brain excitatory peptide, BEP) significantly induced synaptic excitability and possessed some dopaminergic activities in vitro (thus named dopamine neuron stimulating peptides, DNSP)13. Furthermore, the human 11-mer sequence (named DNSP-11) exhibits neurotrophic-like properties13.
Thus, the role of the full proDomain of GDNF, which is a product of proteolytic cleavage of proGDNF, is not clearly understood yet.
human GDNF proDomain (#SPG-100) is a highly pure, synthetic, and biologically active peptide.