Neuronal release of proBDNF
Open accessAbstract
Pro-brain-derived neurotrophic factor (proBDNF) and mature BDNF utilize distinct receptors to mediate divergent neuronal actions. Using new tools to quantitate endogenous BDNF isoforms, we found that mouse neurons secrete both proBDNF and mature BDNF. The highest levels of proBDNF and p75 were observed perinatally and declined, but were still detectable, in adulthood. Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and TrkB.
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mBDNF exerts neuroprotective activity and promotes synaptic plasticity during adulthood.
“A higher level of proBDNF is observed during brain development, while mBDNF exerts neuroprotective activity and promotes synaptic plasticity during adulthood [17,18,19,20,21].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [17]
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Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Teng, H. K., Teng, K. K., Lee, R., Wright, S., Tevar, S., Almeida, R. D., Kermani, P., Torkin, R., Chen, Z.-Y., Lee, F. S., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5123-04.2005 · Cited by 1,013 · see citing works
Self-citationActivation of p75NTR by proBDNF facilitates hippocampal long-term depression
Woo, N. H., Teng, H. K., Siao, C.-J., Chiaruttini, C., Pang, P. T., Milner, T. A., Hempstead, B. L., & Lu, B. (2005) · Nature Neuroscience · doi:10.1038/nn1510 · Cited by 815 · see citing works
Self-citationExcitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator
Tsirka, S. E., Gualandris, A., Amaral, D. G., & Strickland, S. (1995) · Nature · doi:10.1038/377340a0 · Cited by 663 · see citing works
Biosynthesis and Post-translational Processing of the Precursor to Brain-derived Neurotrophic Factor
Mowla, S. J., Farhadi, H. F., Pareek, S., Atwal, J. K., Morris, S. J., Seidah, N. G., & Murphy, R. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008104200 · Cited by 572 · see citing works
Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system
Yan, Q., Rosenfeld, R. D., Matheson, C. R., Hawkins, N., Lopez, O. T., Bennett, L., & Welcher, A. A. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00613-6 · Cited by 498 · see citing works
Chen, Z.-Y., Ieraci, A., Teng, H. K., Dall, H., Meng, C.-X., Herrera, D. G., Nykjær, A., Hempstead, B. L., & Lee, F. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1017-05.2005 · Cited by 401 · see citing works
Self-citationBiosynthesis and processing of endogenous BDNF: CNS neurons store and secrete BDNF, not pro-BDNF
Matsumoto, T., Rauskolb, S., Polack, M., Klose, J., Kolbeck, R., Körte, M., & Barde, Y. (2008) · Nature Neuroscience · doi:10.1038/nn2038 · Cited by 355 · see citing works
Rex, C. S., Lin, C.-Y., Kramár, E. A., Chen, L. Y., Gall, C. M., & Lynch, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4037-06.2007 · Cited by 324 · see citing works
Kolarow, R., Brigadski, T., & Lessmann, V. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0692-07.2007 · Cited by 203 · see citing works
Zheng, M. H., Streck, R. D., Scott, R., et al. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-08-04656.1994 · Cited by 149 · see citing works
Adachi, N., Kohara, K., & Tsumoto, T. (2005) · BMC Neuroscience · doi:10.1186/1471-2202-6-42 · Cited by 78 · see citing works
Wu, Y. J., Krüttgen, A., Möller, J. C., Shine, D., Chan, J. R., Shooter, E. M., & Cosgaya, J. M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20048 · Cited by 60 · see citing works
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Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599 · see citing works
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Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060 · see citing works
Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders
Autry, A. E., & Monteggia, L. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005108 · Cited by 1,390 · see citing works
BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity
Kowiański, P., Lietzau, G., Czuba, E., Waśkow, M., Steliga, A., & Moryś, J. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0510-4 · Cited by 1,359 · see citing works
TrkB signalling pathways in LTP and learning
Minichiello, L. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2738 · Cited by 1,055 · see citing works
BDNF and synaptic plasticity, cognitive function, and dysfunction
Lu, B., Nagappan, G., & Lu, Y. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_9 · Cited by 1,043 · see citing works
Self-citationColucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207777 · Cited by 991 · see citing works
Castrén, E., & Rantamäki, T. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20758 · Cited by 864 · see citing works
Postsynaptic BDNF‐TrkB signaling in synapse maturation, plasticity, and disease
Yoshii, A., & Constantine‐Paton, M. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20765 · Cited by 744 · see citing works
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Gao, L., Zhang, Y., Sterling, K., & Song, W. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00279-0 · Cited by 606 · see citing works
New Insights in the Biology of BDNF Synthesis and Release: Implications in CNS Function
Greenberg, M. E., Xu, B., Lu, B., & Hempstead, B. L. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3566-09.2009 · Cited by 597 · see citing works
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Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., & Niewiadomska, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031170 · Cited by 504 · see citing works
Autocrine BDNF-TrkB signalling within a single dendritic spine
Harward, S. C., Hedrick, N. G., Hall, C. E., Parra-Bueno, P., Milner, T. A., Pan, E., Laviv, T., Hempstead, B. L., Yasuda, R., & McNamara, J. O. (2016) · Nature · doi:10.1038/nature19766 · Cited by 325 · see citing works
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Sasi, M., Vignoli, B., Canossa, M., & Blum, R. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1964-4 · Cited by 324 · see citing works
FAAH genetic variation enhances fronto-amygdala function in mouse and human
Dincheva, I., Drysdale, A. T., Hartley, C. A., Johnson, D. C., Jing, D., King, E. C., Ra, S., Gray, J. M., Yang, R., DeGruccio, A. M., et al. (2015) · Nature Communications · doi:10.1038/ncomms7395 · Cited by 289 · see citing works
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Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity.
Edelmann, E., Leßmann, V., & Brigadski, T. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.043 · Cited by 248 · see citing works
Form follows function: BDNF and its involvement in sculpting the function and structure of synapses
Zagrebelsky, M., & Korte, M. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.029 · Cited by 241 · see citing works
Spontaneous Activity Drives Local Synaptic Plasticity In Vivo
Winnubst, J., Cheyne, J. E., Niculescu, D., & Lohmann, C. (2015) · Neuron · doi:10.1016/j.neuron.2015.06.029 · Cited by 180 · see citing works
Stress effects on BDNF expression: Effects of age, sex, and form of stress
Bath, K. G., Schilit, A., & Lee, F. S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.074 · Cited by 197 · see citing works
Self-citationKoshimizu, H., Kiyosue, K., Hara, T., Hazama, S., Suzuki, S., Uegaki, K., Nagappan, G., Zaitsev, E., Hirokawa, T., Tatsu, Y., et al. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-27 · Cited by 195 · see citing works
Self-citationJe, H. S., Yang, F., Ji, Y., Nagappan, G., Hempstead, B. L., & Lu, B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207767109 · Cited by 188 · see citing works
Self-citationBrain-derived Neurotrophic Factor in Megakaryocytes
Chacón-Fernández, P., Säuberli, K., Colzani, M., Moreau, T., Ghevaert, C., & Barde, Y.-A. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.720029 · Cited by 186 · see citing works
Dunham, J. S., Deakin, J. F. W., Miyajima, F., Payton, A., & Toro, C. T. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.03.008 · Cited by 172 · see citing works
Burbach, J. P. H. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-310-3_1 · Cited by 167 · see citing works
De Vincenti, A. P., Ríos, A. S., Paratcha, G., & Ledda, F. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00135 · Cited by 157 · see citing works
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Woo, E., Sansing, L. H., Arnsten, A. F. T., & Datta, D. (2021) · Chronic Stress · doi:10.1177/24705470211029254 · Cited by 159 · see citing works
TrkB/BDNF signaling pathway and its small molecular agonists in CNS injury
Wang, Y., Liang, J., Xu, B., Yang, J., Wu, Z., & Cheng, L. (2024) · Life Sciences · doi:10.1016/j.lfs.2023.122282 · Cited by 152 · see citing works
Self-citationBDNF control of adult SVZ neurogenesis
Bath, K. G., Akins, M. R., & Lee, F. S. (2012) · Developmental Psychobiology · doi:10.1002/dev.20546 · Cited by 146 · see citing works
Self-citationBDNF signaling during the lifetime of dendritic spines
Zagrebelsky, M., Tacke, C., & Korte, M. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03226-5 · Cited by 147 · see citing works
Mizui, T., Ishikawa, Y., Kumanogoh, H., Lume, M., Matsumoto, T., Hara, T., Yamawaki, S., Takahashi, M., Shiosaka, S., Itami, C., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422336112 · Cited by 141 · see citing works
Hing, B., Sathyaputri, L., & Potash, J. B. (2018) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32616 · Cited by 137 · see citing works
Je, H. S., Yang, F., Ji, Y., Potluri, S., Fu, X.-Q., Luo, Z.-G., Nagappan, G., Chan, J. P., Hempstead, B., Son, Y.-J., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0163-13.2013 · Cited by 128 · see citing works
Self-citationPro-BDNF–induced synaptic depression and retraction at developing neuromuscular synapses
Yang, F., Je, H.-S., Ji, Y., Nagappan, G., Hempstead, B., & Lu, B. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200811147 · Cited by 130 · see citing works
Self-citationNeuropeptides from concept to online database www.neuropeptides.nl
Burbach, J. P. H. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.10.015 · Cited by 123 · see citing works
Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments
Zhao, H., Alam, A., San, C.-Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017) · Brain Research · doi:10.1016/j.brainres.2017.03.029 · Cited by 122 · see citing works
Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain
Gibon, J., & Barker, P. A. (2017) · The Neuroscientist · doi:10.1177/1073858417697037 · Cited by 115 · see citing works
Barker, P. A. (2009) · Nature Neuroscience · doi:10.1038/nn0209-105 · Cited by 110 · see citing works
Deciphering Proneurotrophin Actions
Hempstead, B. L. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_2 · Cited by 106 · see citing works
Self-citationHigh abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons
Andreska, T., Aufmkolk, S., Sauer, M., & Blum, R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00107 · Cited by 100 · see citing works
Warnault, V., Darcq, E., Morisot, N., Phamluong, K., Wilbrecht, L., Massa, S. M., Longo, F. M., & Ron, D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.007 · Cited by 89 · see citing works
Kuzniewska, B., Rejmak, E., Malik, A. R., Jaworski, J., Kaczmarek, L., & Kalita, K. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00008-13 · Cited by 82 · see citing works
Cardenas-Aguayo, M. D. C., Kazim, S. F., Grundke-Iqbal, I., & Iqbal, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053596 · Cited by 73 · see citing works
Diniz, C. R. A. F., Casarotto, P. C., Resstel, L., & Joca, S. R. L. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.04.001 · Cited by 58 · see citing works
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Pardo, C. A., Buckley, A., Thurm, A., Lee, L.-C., Azhagiri, A., Neville, D. M., & Swedo, S. E. (2013) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-5-9 · Cited by 58 · see citing works
Unsain, N., Montroull, L. E., & Mascó, D. H. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06342.x · Cited by 32 · see citing works
Nunes, F., Pochmann, D., Almeida, A. S., Marques, D. M., & Porciúncula, L. D. O. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1000-5 · Cited by 26 · see citing works
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Giannini, A., Bucci, F., Luisi, S., Cela, V., Pluchino, N., Merlini, S., Casarosa, E., Russo, M., Cubeddu, A., Daino, D., et al. (2010) · Journal of Endometriosis · doi:10.1177/228402651000200305 · Cited by 27 · see citing works
- Authors
- Yang, J., Siao, C.-J., Nagappan, G., Marinic, T., Jing, D., McGrath, K., Chen, Z.-Y., Mark, W., Tessarollo, L., Lee, F. S., Lu, B., & Hempstead, B. L.
- Affiliations
- Weill Cornell Medicine (US)
- National Institutes of Health (US)
- Memorial Sloan Kettering Cancer Center (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Hempstead, Barbara L
- Venue
- Nature Neuroscience
- Published
- 2009-01-11
- Volume
- 12
- Issue
- 2
- Pages
- 113-115
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2737352
- OpenAlex
- W2066386560
- Cited by
- 449
- References
- 13
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 20 · 2023: 26 · 2022: 21 · 2021: 33 · 2020: 28 · 2019: 22 · 2018: 22 · 2017: 28 · 2016: 34 · 2015: 22 · 2014: 30 · 2013: 36 · 2012: 31
- FWCI
- 14.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P50MH079513)
- National Institute of Neurological Disorders and Stroke (NS30687, NS52819, R01NS030687, R01NS052819)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- proBDNF, brain-derived neurotrophic factor, neurosecretion, hippocampal neurons, p75 neurotrophin receptor, TrkB receptor, synaptic plasticity, knock-in mice
- MeSH terms
- Animals, Antibodies, Monoclonal, Cell Survival, Cells, Cultured, Hippocampus, Mice, Mutant Strains, Neurons, Protein Precursors, Gene Expression Regulation, Developmental, Brain-Derived Neurotrophic Factor, Receptor, Nerve Growth Factor, Receptor, trkB, Mice, Gene Knock-In Techniques
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