|Precautions||proBDNF Protein (WT-human) is for research use only and not for use in diagnostic or therapeutic procedures.|
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BDNF is a neurotrophic factor produced by proteolytic cleavage of its precursor, proBDNF. The biologically relevant form of the protein was thought to be the mature form, BDNF.1 The actions of BDNF are mediated via the binding to TrkB or p75 .2,3
The precursor form was thought to be important for the correct folding, secretion and trafficking of the mature protein. A single-nucleotide polymorphism ( Val66 to Met) in the pro-domain of the human BDNF gene impairs intracellular trafficking and regulated secretion of BDNF in primary cortical neurons and neurosecretory cells but not in endothelial and vascular cells.4 This has been shown to affect memory and lead to abnormal hippocampal function in humans.5
The finding that proBDNF and not mature BDNF is the preferred ligand for p75, has ushered in a new era which reexamines the biological roles of the two forms.6 Some biological roles for proBDNF have been proposed. It has been shown to be a pro-apoptotic ligand for sympathetic neurons7 expressing both p75 and sortlin, and to be involved in LTD8. On the other hand it has also been shown to elicit prototypical TrkB responses in biological assays, such as TrkB tyrosine phosphorylation, and activation of ERK1/2.9
In brain homogenates a mixture of both, proBDNF and mature BDNF has been found10,11 and in cortical neurons secretion of proBDNF has been shown.7 Binding of both proBDNF and mature BDNF to TrkB has been proposed to be via the R103 residue in the mature portion.9
1 . Bibel, M and Barde, Y.A.(2000)Genes Dev.14,2929
2 . Cahoon-Metzger, S.M.et al. (2001) Dev. Biol.232,246.
3 . Troy, C.M.et al. (2002) J. Biol. Chem.277,34295.
4 . Chen, Z.Y.et al. (2004) J. Neurosci.24,4401.
5 . Egan, M.F.et al.(2003)Cell112,257.
6 . Lee, R.et al.,(2001)Science294,1945.
7 . Teng, H.K.et al. (2005) J. Neurosci.25,5455.
8 . Woo, N.H.et al.(2005)Nat. Neurosci.8,1069.
9 . Fayard, B.et al. (2005) J. Neurosci. Res.80,18.
10 . Michalski, B and Fahnestock, M. (2003)Mol. Brain Res.111,148.
11 . Zhou, X.F.et al.(2004)J. Neurochem.91,704.
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