GDNF proDomain Protein (WT-human)

Provided below are standard protocols that you may find useful for product applications.

Background

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 motoneurons^2,3, 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 neurons^9,10.
 
Recently, it has been hypothesized that functional, carboxy-terminally amidated peptides are processed from the GDNF precursor upon proteolytic cleavage by furin-like endopeptidase^11,12,13. 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.

References

1 . Airaksinen, M.S.et al.(2002)Nat. Rev. Neurosci.3,383.
2 . Henderson, C.E. et al.(1994)Science266,1062.
3 . Houenou, L.J.et al.(1996)Cell. Tissue Res.286,219.
4 . Kobayashi, M.et al.(2000)Neuroreport11,2541.
5 . Tomac, A.et al.(1995)Nature373,335.
6 . Zhou, F.Q.et al.(2003)Cell113,814.
7 . Lin, L.F.et al.(1993)Science260,1130.
8 . Matheson, C.R.et al.(1997)Neuroreport8,1739.
9 . Brundin, P.(2002)Brain125,2149.
10 . Grondin, R.et al.(1998)J. Neurol.245,P35.
11 . Bradley, L.H.et al.(2010)PLoS ONE5,e9752.
12 . Immonen, T.et al.(2008)Exp. Neurol.210,793.
13 . Kelps, K.A.et al.(2011)Neuropeptides45,213.