Cell and Tissue Research

, Volume 377, Issue 1, pp 73–79 | Cite as

BDNF pro-peptide: physiological mechanisms and implications for depression

  • Masami KojimaEmail author
  • Konomi Matsui
  • Toshiyuki Mizui


Most growth factors are synthesized as precursors and biologically active forms are generated by proteolytic cleavage of the pro-domain. However, the biological functions of pro-domains are ill-defined. New roles were recently reported for the pro-domain of brain-derived neurotrophic factor (BDNF), a well-known growth factor in the brain. Interestingly, the pro-domain of BDNF (BDNF pro-peptide) is localized at presynaptic termini, where it facilitates long-term depression (LTD) in hippocampal slices, implicating it as a novel synaptic modulator. BDNF binds its pro-peptide with high affinity in a pH-dependent manner and when bound to BDNF, the BDNF pro-peptide cannot facilitate hippocampal LTD, representing a new mechanism of regulation. The BDNF pro-peptide is present in human cerebrospinal fluid (CSF) and levels were significantly lower in patients with major depressive disorder (MDD) than in controls. Notably, male MDD patients exhibit significantly lower levels of CSF pro-peptide than females. These findings demonstrate that the BDNF pro-peptide is a biologically important synaptic modulator and is associated with MDD, particularly in males.


BDNF pro-peptide Proteolytic processing Long-term depression Synaptic modulator Major depressive disorder 



We thank Dr. Haruko Kumanogoh for the preparation of Figure 1.

Funding information

This work was supported by the Japan Science and Technology Agency “Core Research for Evolutional Science and Technology (CREST)” (T.M. and M.K).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Masami Kojima
    • 1
    • 2
    Email author
  • Konomi Matsui
    • 1
    • 2
  • Toshiyuki Mizui
    • 1
  1. 1.Biomedical Research Institute (BMD), National Institute of Advanced Industrial Science and Technology (AIST)OsakaJapan
  2. 2.Graduate School of Frontier BiosciencesOsaka UniversitySuitaJapan

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