Recombinant human Val66Met proBDNF (cleavage resistant) protein

Val66Met proBrain-Derived Neurotrophic Factor (Mut-human)
A Neurotrophic Factor
    Cat #: B-456
    Alternative Name Val66Met proBrain-Derived Neurotrophic Factor (Mut-human)
  • Lyophilized Powder
  • Bioassay Tested
  • Sterile & Endotoxin Free
  • Origin Human.
    Source Recombinant, E. coli
    MW: 51.45 kDa., dimer
    Endotoxin Level <0.1 EU per 1 µg of the protein by the LAL method.
    Purity: >98% (HPLC)
    Form Lyophilized from a 0.2 µm filtered solution.
    Effective concentration 0.1-10 nM.
    Activity Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that bind p75NTR as well as TrkB receptors1,2 and supports the survival of many cell types3-8. proBDNF has been shown to be a pro-apoptotic ligand for sympathetic neurons9 expressing both p75NTR and sortilin, and to be involved in long-term potentiation (LTP) stage of the memory-related modifications in synaptic transmission10.
    Shipping and storage Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C.
    Solubility Any other aqueous buffer. Centrifuge all product preparations before use (10000 x g 5 min).
    Storage of solutions Up to two weeks at 4°C or three months at -20°C.
      • Recombinant human Val66Met proBDNF (cleavage resistant) protein
        Alomone Labs Recombinant human Val66Met proBDNF (cleavage resistant) protein mediates ERK1/2 phosphorylation as Recombinant human proBDNF (cleavage resistant) protein in TrkB transfected HEK293 cells.
        Transfected HEK293 cells were serum depleted for 2 hr and then challenged with or without Recombinant human Val66Met proBDNF (cleavage resistant) protein (#B-456) or Recombinant human proBDNF (cleavage resistant) protein (#B-256) for 10 min. The cell proteins were resolved by SDS-PAGE and detected with anti-phospho-ERK1/2 antibody.
    References - Scientific background
    • 1. Tolkovsky, A. (1997) Trends Neurosi. 20, 1.
    • 2. Jing, S. et al. (1992) Neuron 9, 1067.
    • 3. Acheson, A. et al. (1995) Nature 374, 450.
    • 4. Morse, J.K. et al. (1993) J. Neurosci. 13, 4146.
    • 5. Hyman, C. et al. (1991) Nature 350, 230.
    • 6. Friedman, B. et al. (1995) J. Neurosci. 15, 1044.
    • 7. Meyer, M. et al. (1992) J. Cell Biol. 119, 45.
    • 8. Koliatsos, V.E. et al. (1993) Neuron 10, 359.
    • 9. Egan, M.F. et al. (2003) Cell 112, 257.
    • 10. Seidah, N.G. et al. (1996) FEBS Lett. 379, 247.
    • 11. Teng, H.K. et al. (2005) J. Neurosci. 25, 5455.
    • 12. Woo, N.H. et al. (2005) Nat. Neurosci. 8, 1069.
    • 13. Korte, M. et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 8856.
    • 14. Lyons, W.E. et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 15239.
    • 15. Post, R.M. (2007) J. Psychiatric Res. 41, 979.
    • 16. Ho, B.C. et al. (2006) Arch. Gen. Psychiatry 63, 731.
    • 17. Rosa, A. et al. (2006) Am. J. Med. Gen. B Neuropsych. Gen. 141B, 135.
    • 18. Hashimoto, K. (2007) BioEssays 29, 116.
    • 19. Chen Z.Y. et al. (2006) Science 314, 140.
    • 20. Kent, L. et al. (2005) Mol. Psychiatry 10, 939.
    • 21. Sanchez-Mora C. et al. (2010) Am. J. Med. Gen. B Neuropsych. Gen. 153B, 512.
      • Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that bind p75NTR as well as TrkB receptors1,2. BDNF supports the survival of many cell types3-8 and also modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals9.

        The BDNF gene, like other peptide growth factors, encodes a precursor peptide (proBDNF), which is proteolytically cleaved to form the mature protein10. proBDNF has been shown to be a pro-apoptotic ligand for sympathetic neurons expressing both p75NTR and sortilin11, and to be involved in long-term potentiation (LTP) stage of the memory-related modifications in synaptic transmission12.

        A nonconservative single nucleotide polymorphism (SNP) in the human BDNF gene has been identified at nucleotide 196 (G/A) producing an amino acid substitution (Valine to Methionine) at codon 66 (Val66Met, rs 6265). Although located in the 5' pro-BDNF region, this SNP resulted in striking deficits in the cellular distribution and regulated secretion of the mature protein, BDNF and hence in corresponding alterations of human hippocampal function and episodic memory in vivo9.

        Egan M.F. et al demonstrated the molecular mechanisms that control activity-dependent BDNF secretion and showed that depolarization-dependent secretion of BDNF in hippocampal neurons is significantly impaired when this Val66Met SNP occurs. Using double-staining techniques, they demonstrated that Val-BDNF-containing secretory granules are colocalized with synaptophysin, a marker for synapses. In contrast, Val66Met-BDNF aggregates are accumulated in the cell body and rarely colocalize with synaptophysin. This suggests that even if it can be secreted in small amounts near the cell body through the constitutive pathway, the Met-BDNF protein cannot be secreted at synapses9. Studies of heterozygote BDNF knockout rodents, who presumably have intermediate BDNF levels, demonstrate clear physiological13 and behavioral14 abnormalities, suggesting that secretion levels are critical.

        Multiple studies over the recent decades in humans, in vivo in animal models and in vitro found an association between the Val66Met polymorphism and bipolar and unipolar disorders15, Schizophrenia16,17, anxiety-related behavior18,19 and controversial association with ADHD20,21.

        The data emerged from the analysis of the Val66Met phenotype in various syndromes and diseases reveal the importance of the pro-region of the BDNF polypeptide, particular Valine66 and perhaps the nearby sequence, in intracellular trafficking and secretion of BDNF.

    Net Peptide Content: 100%
    Last update: 02/09/2019

    Recombinant human Val66Met proBDNF (cleavage resistant) protein (# B-456) is a highly pure, recombinant, and biologically active protein.

    For research purposes only, not for human use