BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met
Open accessAbstract
Significance: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits biological effects on synaptic plasticity. BDNF is initially synthesized as precursor proBDNF, and then the BDNF pro-peptide is simultaneously produced from the precursor protein. However, the physiological functions of the pro-peptide are largely unknown. Here, we demonstrate that the BDNF pro-peptide is a facilitator of hippocampal long-term depression (LTD), requiring the activation of GluN2B-containing NMDA-type receptors and the pan-neurotrophin receptor p75 NTR . Second, a common BDNF polymorphism substitutes valine for methionine at amino acid position 66 (Val66Met) in the pro-peptide of BDNF and impairs memory function. Unexpectedly, the pro-peptide with Met mutation completely inhibits hippocampal LTD. These findings provide insights into the physiological role of the BDNF pro-peptide in the brain.
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The BDNF pro-peptide released from pro-BDNF has biological effects on its own.
“In addition, the BDNF pro-peptide that is released from pro-BDNF has recently been shown to possess biological effects on its own84,85.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [84]
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“Recent studies have shown the presence of BDNF pro-peptide in rodent brain, and membrane depolarization induced BDNF pro-peptide secretion in dissociated neuronal cultures.15–17 Further, BDNF pro-peptide was shown to induce acute growth cone retraction,16 and facilitate LTD.17 In this study, using a newly generated BD…”
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- Authors
- Mizui, T., Ishikawa, Y., Kumanogoh, H., Lume, M., Matsumoto, T., Hara, T., Yamawaki, S., Takahashi, M., Shiosaka, S., Itami, C., Uegaki, K., Saarma, M., & Kojima, M.
- Affiliations
- Japan Science and Technology Agency (JP)
- Maebashi Institute of Technology (JP)
- University of Helsinki (FI)
- Hiroshima University (JP)
- Saitama Medical University (JP)
- Institute of Biotechnology, University of Helsinki, FIN-00014, Helsinki, Finland;
- Corresponding author
- Kojima, Masami
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-05-26
- Volume
- 112
- Issue
- 23
- Pages
- E3067-74
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4466729
- OpenAlex
- W1595936241
- Cited by
- 141
- References
- 46
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 16 · 2019: 19 · 2018: 15 · 2017: 14 · 2016: 11 · 2015: 2
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- KAKEN-HI, the Ministry of Education, Culture, Sports, Science and Technology of Japan (40344171)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- brain-derived neurotrophic factor, BDNF Val66Met polymorphism, NMDA receptor, GluN2B, p75 neurotrophin receptor, AMPA receptor endocytosis, synaptic plasticity, precursor protein processing
- MeSH terms
- Animals, Hippocampus, Humans, Methionine, Polymorphism, Genetic, Protein Precursors, Valine, Mice, Knockout, Brain-Derived Neurotrophic Factor, Long-Term Synaptic Depression, Mice, Rats
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