Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor

Edelbrock, Alexandra N.; Àlvarez, Zaida; Simkin, Dina; Fyrner, Timmy; Chin, Stacey M.; Sato, Kohei; Kiskinis, Evangelos; Stupp, Samuel I.

doi:10.1021/acs.nanolett.8b02317

Title: Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor

Journal Article · Thu Sep 13 00:00:00 EDT 2018 · Nano Letters

DOI:https://doi.org/10.1021/acs.nanolett.8b02317· OSTI ID:1482234

Edelbrock, Alexandra N. ^[1]; Àlvarez, Zaida ^[2]; Simkin, Dina ^[3];

^[2]; Chin, Stacey M. ^[4];

^[5]; Kiskinis, Evangelos ^[3];

^[6]

Northwestern Univ., Evanston, IL (United States); Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst.
Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst.
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst.; Northwestern Univ., Evanston, IL (United States)
Northwestern Univ., Evanston, IL (United States); Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst. and Dept. of Medicine

Brain-derived neurotrophic factor (BDNF), a neurotrophin that binds specifically to the tyrosine kinase B (TrkB) receptor, has been shown to promote neuronal differentiation, maturation, and synaptic plasticity in the central nervous system (CNS) during development or after injury and onset of disease. Unfortunately, native BDNF protein-based therapies have had little clinical success due to their suboptimal pharmacological properties. In the past 20 years, BDNF mimetic peptides have been designed with the purpose of activating certain cell pathways that mimic the functional activity of native BDNF, but the interaction of mimetic peptides with cells can be limited due to the conformational specificity required for receptor activation. We report here on the incorporation of a BDNF mimetic sequence into a supramolecular peptide amphiphile filamentous nanostructure capable of activating the BDNF receptor TrkB and downstream signaling in primary cortical neurons in vitro. Interestingly, we found that this BDNF mimetic peptide is only active when displayed on a peptide amphiphile supramolecular nanostructure. We confirmed that increased neuronal maturation is linked to TrkB signaling pathways by analyzing the phosphorylation of downstream signaling effectors and tracking electrical activity over time. Furthermore, three-dimensional gels containing the BDNF peptide amphiphile (PA) nanostructures encourage cell infiltration while increasing functional maturation. Our findings suggest that the BDNF mimetic PA nanostructure creates a highly bioactive matrix that could serve as a biomaterial therapy in injured regions of the CNS. As such, this new strategy has the potential to induce endogenous cell infiltration and promote functional neuronal maturation through the presentation of the BDNF mimetic signal.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); US Army Research Office (ARO); US Army Medical Research Materiel Command; National Science Foundation (NSF); National Cancer Institute (NCI); State of Illinois; International Institute for Nanotechnology (IIN); Northwestern University; E.I. DuPont de Nemours & Co.; The Dow Chemical Company; National Institutes of Health (NIH); National Institute of Biomedical Imaging and Bioengineering (NIBIB); Les Turner ALS Foundation; Muscular Dystrophy Association; Dravet Foundation; National Institute of Neurological Disorders and Stroke (NINDS); Beatriu de Pinós Fellowship; Paralyzed Veterans of America (PVA) Research Foundation

Grant/Contract Number:: NCI CA060553; AC02-06CH11357; 5R01EB003806-07; PVA17_RF_0008

OSTI ID:: 1482234

Journal Information:: Nano Letters, Vol. 18, Issue 10; ISSN 1530-6984

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 66 works

Citation information provided by
Web of Science

References (72)

Sulfated glycopeptide nanostructures for multipotent protein activation Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng Nature Nanotechnology, Vol. 12, Issue 8 https://doi.org/10.1038/nnano.2017.109	journal	June 2017
BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury Lu, P.; Jones, L.; Tuszynski, M. Experimental Neurology, Vol. 191, Issue 2 https://doi.org/10.1016/j.expneurol.2004.09.018	journal	February 2005
The BDNF effects on dendritic spines of mature hippocampal neurons depend on neuronal activity Kellner, Yves; GÃ¶decke, Nina; Dierkes, Tobias Frontiers in Synaptic Neuroscience, Vol. 6 https://doi.org/10.3389/fnsyn.2014.00005	journal	March 2014
Brain-Derived Neurotrophic Factor Is Required for the Maintenance of Cortical Dendrites Gorski, Jessica A.; Zeiler, Steven R.; Tamowski, Susan The Journal of Neuroscience, Vol. 23, Issue 17 https://doi.org/10.1523/JNEUROSCI.23-17-06856.2003	journal	July 2003
TrkB-enhancer facilitates functional recovery after traumatic brain injury Marshall, John; Szmydynger-Chodobska, Joanna; Rioult-Pedotti, Mengia S. Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-11316-8	journal	September 2017
A Brain-Derived Neurotrophic Factor-Based p75 ^NTR Peptide Mimetic Ameliorates Experimental Autoimmune Neuritis Induced Axonal Pathology and Demyelination Gonsalvez, David G.; Tran, Giang; Fletcher, Jessica L. eneuro, Vol. 4, Issue 3 https://doi.org/10.1523/ENEURO.0142-17.2017	journal	May 2017
Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair Webber, M. J.; Tongers, J.; Newcomb, C. J. Proceedings of the National Academy of Sciences, Vol. 108, Issue 33 https://doi.org/10.1073/pnas.1016546108	journal	August 2011
Design of a Conformationally Defined and Proteolytically Stable Circular Mimetic of Brain-derived Neurotrophic Factor Fletcher, Jordan M.; Morton, Craig J.; Zwar, Richard A. Journal of Biological Chemistry, Vol. 283, Issue 48 https://doi.org/10.1074/jbc.M802789200	journal	November 2008
Instructing cells with programmable peptide DNA hybrids Freeman, Ronit; Stephanopoulos, Nicholas; Álvarez, Zaida Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15982	journal	July 2017
Electrostatic Control of Bioactivity Goldberger, Joshua E.; Berns, Eric J.; Bitton, Ronit Angewandte Chemie International Edition, Vol. 50, Issue 28 https://doi.org/10.1002/anie.201100202	journal	May 2011
Neurotrophins and their receptors: A convergence point for many signalling pathways Chao, Moses V. Nature Reviews Neuroscience, Vol. 4, Issue 4 https://doi.org/10.1038/nrn1078	journal	April 2003
Neurotrophin regulation of neural circuit development and function Park, Hyungju; Poo, Mu-ming Nature Reviews Neuroscience, Vol. 14, Issue 1 https://doi.org/10.1038/nrn3379	journal	December 2012
The MAP2/Tau family of microtubule-associated proteins Dehmelt, Leif; Halpain, Shelley Genome Biology, Vol. 6, Issue 1, p. 204 https://doi.org/10.1186/gb-2004-6-1-204	journal	December 2004
Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers Hartgerink, Jeffrey D.; Beniash, Elia; Stupp, Samuel I. Science, Vol. 294, Issue 5547, p. 1684-1688 https://doi.org/10.1126/science.1063187	journal	November 2001
Peptides derived from the solvent-exposed loops 3 and 4 of BDNF bind TrkB and p75 ^NTR receptors and stimulate neurite outgrowth and survival Fobian, Kristina; Owczarek, Sylwia; Budtz, Christian Journal of Neuroscience Research https://doi.org/10.1002/jnr.22285	journal	January 2009
Functional Supramolecular Polymers Aida, T.; Meijer, E. W.; Stupp, S. I. Science, Vol. 335, Issue 6070 https://doi.org/10.1126/science.1205962	journal	February 2012
Converting a Peptide into a Drug: Strategies to Improve Stability and Bioavailability Adessi, Celine; Soto, Claudio Current Medicinal Chemistry, Vol. 9, Issue 9 https://doi.org/10.2174/0929867024606731	journal	May 2002
BDNF/ TrkB interaction regulates migration of SVZ precursor cells via PI3-K and MAP-K signalling pathways: BDNF regulates SVZ neuroblast migration Chiaramello, S.; Dalmasso, G.; Bezin, L. European Journal of Neuroscience, Vol. 26, Issue 7 https://doi.org/10.1111/j.1460-9568.2007.05818.x	journal	September 2007
A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration Lu, Jiaju; Sun, Xun; Yin, Heyong Nano Research, Vol. 11, Issue 9 https://doi.org/10.1007/s12274-018-2041-9	journal	March 2018
A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells Berns, Eric J.; Álvarez, Zaida; Goldberger, Joshua E. Acta Biomaterialia, Vol. 37 https://doi.org/10.1016/j.actbio.2016.04.010	journal	June 2016
Fine tuning neuronal targeting of nanoparticles by adjusting the ligand grafting density and combining PEG spacers of different length Pereira Gomes, Carla; Leiro, Victoria; Ferreira Lopes, Cátia Daniela Acta Biomaterialia, Vol. 78 https://doi.org/10.1016/j.actbio.2018.08.005	journal	September 2018
Energy landscapes and functions of supramolecular systems Tantakitti, Faifan; Boekhoven, Job; Wang, Xin Nature Materials, Vol. 15, Issue 4 https://doi.org/10.1038/nmat4538	journal	January 2016
Neurotrophins: Roles in Neuronal Development and Function Huang, Eric J.; Reichardt, Louis F. Annual Review of Neuroscience, Vol. 24, Issue 1 https://doi.org/10.1146/annurev.neuro.24.1.677	journal	March 2001
MAPK cascade signalling and synaptic plasticity Thomas, Gareth M.; Huganir, Richard L. Nature Reviews Neuroscience, Vol. 5, Issue 3 https://doi.org/10.1038/nrn1346	journal	March 2004
Structure-Activity Relationships of Conformationally Constrained Peptide Analogues of Loop 2 of Brain-Derived Neurotrophic Factor O'Leary, P. D.; Hughes, R. A. Journal of Neurochemistry, Vol. 70, Issue 4 https://doi.org/10.1046/j.1471-4159.1998.70041712.x	journal	April 1998
Balance and Stability of Synaptic Structures during Synaptic Plasticity Meyer, Daniel; Bonhoeffer, Tobias; Scheuss, Volker Neuron, Vol. 82, Issue 2 https://doi.org/10.1016/j.neuron.2014.02.031	journal	April 2014
Neuronal activity alters BDNF-TrkB signaling kinetics and downstream functions Guo, Wei; Ji, Yuanyuan; Wang, Shudan Journal of Cell Science https://doi.org/10.1242/jcs.139964	journal	January 2014
Interface Immobilization Chemistry of c RGD‐based Peptides Regulates Integrin Mediated Cell Adhesion Pallarola, Diego; Bochen, Alexander; Boehm, Heike Advanced Functional Materials, Vol. 24, Issue 7 https://doi.org/10.1002/adfm.201302411	journal	October 2013
New Directions for Half-Life Extension of Protein Therapeutics: The Rise of Antibody Fc Domains and Fragments Wang, Lili; Ying, Tianlei Current Pharmaceutical Biotechnology, Vol. 17, Issue 15 https://doi.org/10.2174/1389201017666160823144032	journal	December 2016
Transplantation of RADA16-BDNF peptide scaffold with human umbilical cord mesenchymal stem cells forced with CXCR4 and activated astrocytes for repair of traumatic brain injury Shi, W.; Huang, C. J.; Xu, X. D. Acta Biomaterialia, Vol. 45 https://doi.org/10.1016/j.actbio.2016.09.001	journal	November 2016
Supramolecular Assembly of Peptide Amphiphiles Hendricks, Mark P.; Sato, Kohei; Palmer, Liam C. Accounts of Chemical Research, Vol. 50, Issue 10 https://doi.org/10.1021/acs.accounts.7b00297	journal	September 2017
Binding of brain-derived neurotrophic factor to the nerve growth factor receptor Rodriguez-Tebar, Alfredo; Dechant, Georg; Barde, Yves-Alain Neuron, Vol. 4, Issue 4 https://doi.org/10.1016/0896-6273(90)90107-Q	journal	April 1990
TrkB and TrkC Signaling Are Required for Maturation and Synaptogenesis of Hippocampal Connections Martı́nez, Albert; Alcántara, Soledad; Borrell, Vı́ctor The Journal of Neuroscience, Vol. 18, Issue 18 https://doi.org/10.1523/JNEUROSCI.18-18-07336.1998	journal	September 1998
Serum-free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus Brewer, G. J. Journal of Neuroscience Research, Vol. 42, Issue 5 https://doi.org/10.1002/jnr.490420510	journal	December 1995
Brain-Derived Neurotrophic Factor Stimulates Energy Metabolism in Developing Cortical Neurons Burkhalter, Julia; Fiumelli, Hubert; Allaman, Igor The Journal of Neuroscience, Vol. 23, Issue 23 https://doi.org/10.1523/JNEUROSCI.23-23-08212.2003	journal	September 2003
Brain-derived neurotrophic factor and the development of structural neuronal connectivity Cohen-Cory, Susana; Kidane, Adhanet H.; Shirkey, Nicole J. Developmental Neurobiology https://doi.org/10.1002/dneu.20774	journal	January 2010
Growth Factors, Matrices, and Forces Combine and Control Stem Cells Discher, D. E.; Mooney, D. J.; Zandstra, P. W. Science, Vol. 324, Issue 5935 https://doi.org/10.1126/science.1171643	journal	June 2009
Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines Tanaka, J. -i.; Horiike, Y.; Matsuzaki, M. Science, Vol. 319, Issue 5870 https://doi.org/10.1126/science.1152864	journal	March 2008
Neurotrophins Stimulate Chemotaxis of Embryonic Cortical Neurons Behar, T. N.; Dugich-Djordjevic, M. M.; Li, Y-X. European Journal of Neuroscience, Vol. 9, Issue 12 https://doi.org/10.1111/j.1460-9568.1997.tb01685.x	journal	December 1997
Trk Receptors: Roles in Neuronal Signal Transduction Huang, Eric J.; Reichardt, Louis F. Annual Review of Biochemistry, Vol. 72, Issue 1 https://doi.org/10.1146/annurev.biochem.72.121801.161629	journal	June 2003
Nanofibrous scaffolds releasing a small molecule BDNF-mimetic for the re-direction of endogenous neuroblast migration in the brain Fon, Deniece; Zhou, Kun; Ercole, Francesca Biomaterials, Vol. 35, Issue 9 https://doi.org/10.1016/j.biomaterials.2013.12.016	journal	March 2014
A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis Ochs, Günter; Penn, Richard D.; York, Michelle Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, Vol. 1, Issue 3 https://doi.org/10.1080/14660820050515197	journal	January 2000
Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons Rubert Pérez, Charles M.; Álvarez, Zaida; Chen, Feng ACS Biomaterials Science & Engineering, Vol. 3, Issue 9 https://doi.org/10.1021/acsbiomaterials.7b00347	journal	June 2017
Modified low molecular weight cyclic peptides as mimetics of BDNF with improved potency, proteolytic stability and transmembrane passage in vitro Fletcher, Jordan M.; Hughes, Richard A. Bioorganic & Medicinal Chemistry, Vol. 17, Issue 7 https://doi.org/10.1016/j.bmc.2009.02.053	journal	April 2009
Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor Fletcher, Jordan M.; Hughes, Richard A. Journal of Peptide Science, Vol. 12, Issue 8 https://doi.org/10.1002/psc.760	journal	January 2006
Surfaces modified with covalently-immobilized adhesive peptides affect fibroblast population motility Olbrich, Kevin C.; Andersen, Thomas T.; Blumenstock, Frank A. Biomaterials, Vol. 17, Issue 8 https://doi.org/10.1016/0142-9612(96)81412-8	journal	January 1996
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease Nagahara, Alan H.; Merrill, David A.; Coppola, Giovanni Nature Medicine, Vol. 15, Issue 3 https://doi.org/10.1038/nm.1912	journal	February 2009
Presentation and Recognition of Biotin on Nanofibers Formed by Branched Peptide Amphiphiles Guler, Mustafa O.; Soukasene, Stephen; Hulvat, James F. Nano Letters, Vol. 5, Issue 2 https://doi.org/10.1021/nl048238z	journal	February 2005
TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes oligodendrocyte myelination Wong, Agnes W.; Giuffrida, Lauren; Wood, Rhiannon Molecular and Cellular Neuroscience, Vol. 63 https://doi.org/10.1016/j.mcn.2014.10.002	journal	November 2014
Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation Sleep, Eduard; Cosgrove, Benjamin D.; McClendon, Mark T. Proceedings of the National Academy of Sciences, Vol. 114, Issue 38 https://doi.org/10.1073/pnas.1708142114	journal	September 2017
Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson’s disease patients with mild cognitive impairment Costa, Alberto; Peppe, Antonella; Carlesimo, Giovanni Augusto Frontiers in Behavioral Neuroscience, Vol. 9 https://doi.org/10.3389/fnbeh.2015.00253	journal	September 2015
β1-Integrin and Integrin Linked Kinase Regulate Astrocytic Differentiation of Neural Stem Cells Pan, Liuliu; North, Hilary A.; Sahni, Vibhu PLoS ONE, Vol. 9, Issue 8 https://doi.org/10.1371/journal.pone.0104335	journal	August 2014
Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons Ji, Yuanyuan; Pang, Petti T.; Feng, Linyin Nature Neuroscience, Vol. 8, Issue 2 https://doi.org/10.1038/nn1381	journal	January 2005
Potential therapeutic uses of BDNF in neurological and psychiatric disorders Nagahara, Alan H.; Tuszynski, Mark H. Nature Reviews Drug Discovery, Vol. 10, Issue 3 https://doi.org/10.1038/nrd3366	journal	March 2011
Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents Massa, Stephen M.; Yang, Tao; Xie, Youmei Journal of Clinical Investigation, Vol. 120, Issue 5 https://doi.org/10.1172/JCI41356	journal	May 2010
Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease Yoshii, Akira; Constantine-Paton, Martha Developmental Neurobiology https://doi.org/10.1002/dneu.20765	journal	January 2010
A double-blind placebo-controlled clinical trial of recombinant human brain-derived neurotrophic factor (rhBDNF) in diabetic polyneuropathy Wellmer, Andreas; Misra, Vijay Peter; Sharief, Mohammad K. Journal of the Peripheral Nervous System, Vol. 6, Issue 4 https://doi.org/10.1046/j.1529-8027.2001.01019.x	journal	December 2001
Neurotrophin-3 and Brain-Derived Neurotrophic Factor Induce Oligodendrocyte Proliferation and Myelination of Regenerating Axons in the Contused Adult Rat Spinal Cord McTigue, Dana M.; Horner, Philip J.; Stokes, Bradford T. The Journal of Neuroscience, Vol. 18, Issue 14 https://doi.org/10.1523/JNEUROSCI.18-14-05354.1998	journal	July 1998
Transient Growth Factor Delivery Sustains Regenerated Axons after Spinal Cord Injury Blesch, A.; Tuszynski, M. H. Journal of Neuroscience, Vol. 27, Issue 39 https://doi.org/10.1523/JNEUROSCI.1903-07.2007	journal	September 2007
BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases Lu, Bai; Nagappan, Guhan; Guan, Xiaoming Nature Reviews Neuroscience, Vol. 14, Issue 6 https://doi.org/10.1038/nrn3505	journal	May 2013
Motoneuron BDNF/TrkB signaling enhances functional recovery after cervical spinal cord injury Mantilla, Carlos B.; Gransee, Heather M.; Zhan, Wen-Zhi Experimental Neurology, Vol. 247 https://doi.org/10.1016/j.expneurol.2013.04.002	journal	September 2013
The yin and yang of neurotrophin action Lu, Bai; Pang, Petti T.; Woo, Newton H. Nature Reviews Neuroscience, Vol. 6, Issue 8 https://doi.org/10.1038/nrn1726	journal	August 2005
Brain-Derived Neurotrophic Factor Administration Mediated Oligodendrocyte Differentiation and Myelin Formation in Subcortical Ischemic Stroke Ramos-Cejudo, Jaime; Gutiérrez-Fernández, María; Otero-Ortega, Laura Stroke, Vol. 46, Issue 1 https://doi.org/10.1161/STROKEAHA.114.006692	journal	January 2015
The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease Budni, Josiane; Bellettini-Santos, Tatiani; Mina, Francielle Aging and Disease, Vol. 6, Issue 5 https://doi.org/10.14336/AD.2015.0825	journal	January 2015
Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses Okada, Daisuke; Yamagishi, Shunichi; Sugiyama, Hiroyuki Neuroscience Letters, Vol. 100, Issue 1-3 https://doi.org/10.1016/0304-3940(89)90674-5	journal	May 1989
Design of Potent Peptide Mimetics of Brain-derived Neurotrophic Factor O'Leary, Paul D.; Hughes, Richard A. Journal of Biological Chemistry, Vol. 278, Issue 28 https://doi.org/10.1074/jbc.M303209200	journal	July 2003
Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers Silva, Gabriel A.; Czeisler, Catherine; Niece, Krista L. Science, Vol. 303, Issue 5662, p. 1352-1355 https://doi.org/10.1126/science.1093783	journal	February 2004
Purification of a new neurotrophic factor from mammalian brain. Barde, Y. A.; Edgar, D.; Thoenen, H. The EMBO Journal, Vol. 1, Issue 5 https://doi.org/10.1002/j.1460-2075.1982.tb01207.x	journal	May 1982
Epitope topography controls bioactivity in supramolecular nanofibers Sur, Shantanu; Tantakitti, Faifan; Matson, John B. Biomaterials Science, Vol. 3, Issue 3 https://doi.org/10.1039/C4BM00326H	journal	January 2015
Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons Ji, Yuanyuan; Lu, Yuan; Yang, Feng Nature Neuroscience, Vol. 13, Issue 3 https://doi.org/10.1038/nn.2505	journal	February 2010
Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches Thoenen, Hans; Sendtner, Michael Nature Neuroscience, Vol. 5, Issue S11 https://doi.org/10.1038/nn938	journal	October 2002
Signaling Mechanisms Mediating BDNF Modulation of Synaptic Plasticity in the Hippocampus Gottschalk, Wolfram A.; Jiang, Hao; Tartaglia, Nicole Learning & Memory, Vol. 6, Issue 3 https://doi.org/10.1101/lm.6.3.243	journal	May 1999

Cited By (8)

Using Self-Assembling Peptides to Integrate Biomolecules into Functional Supramolecular Biomaterials Liu, Renjie; Hudalla, Gregory A. Molecules, Vol. 24, Issue 8 https://doi.org/10.3390/molecules24081450	journal	April 2019
In Situ Self‐Assembled Nanofibers Precisely Target Cancer‐Associated Fibroblasts for Improved Tumor Imaging Zhao, Xiao‐Xiao; Li, Li‐Li; Zhao, Ying Angewandte Chemie, Vol. 131, Issue 43 https://doi.org/10.1002/ange.201908185	journal	September 2019
β-Galactosidase instructed supramolecular hydrogelation for selective identification and removal of senescent cells Xu, Tengyan; Cai, Yanbin; Zhong, Xinglong Chemical Communications, Vol. 55, Issue 50 https://doi.org/10.1039/c9cc03056e	journal	January 2019
Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma Zhao, Xiyue; Liu, Xiaoyu; Zhang, Pengcheng Acta Pharmaceutica Sinica B, Vol. 9, Issue 5 https://doi.org/10.1016/j.apsb.2019.06.001	journal	September 2019
Pep‐Lipid Cubosomes and Vesicles Compartmentalized by Micelles from Self‐Assembly of Multiple Neuroprotective Building Blocks Including a Large Peptide Hormone PACAP‐DHA Angelova, Angelina; Drechsler, Markus; Garamus, Vasil M. ChemNanoMat, Vol. 5, Issue 11 https://doi.org/10.1002/cnma.201900468	journal	September 2019
In Situ Self‐Assembled Nanofibers Precisely Target Cancer‐Associated Fibroblasts for Improved Tumor Imaging Zhao, Xiao‐Xiao; Li, Li‐Li; Zhao, Ying Angewandte Chemie International Edition, Vol. 58, Issue 43 https://doi.org/10.1002/anie.201908185	journal	October 2019
Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway Yan, Tingxu; He, Bosai; Xu, Mengjie Phytotherapy Research, Vol. 33, Issue 4 https://doi.org/10.1002/ptr.6300	journal	January 2019
Advanced Bottom‐Up Engineering of Living Architectures Gaspar, Vítor M.; Lavrador, Pedro; Borges, João Advanced Materials, Vol. 32, Issue 6 https://doi.org/10.1002/adma.201903975	journal	December 2019

Figures / Tables (5)

Similar Records

BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

Journal Article · Fri Aug 24 00:00:00 EDT 2012 · Biochemical and Biophysical Research Communications · OSTI ID:1482234

Brunetto de Farias, Caroline; Heinen, Tiago Elias; Pereira dos Santos, Rafael; +3 more

A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells

Journal Article · Thu Apr 07 00:00:00 EDT 2016 · Acta Biomaterialia · OSTI ID:1482234

Berns, Eric J.; Álvarez, Zaida; Goldberger, Joshua E.; +4 more

Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization

Journal Article · Sun Jan 01 00:00:00 EST 1995 · Genomics · OSTI ID:1482234

Edelhoff, S; Disteche, C M; Lai, C

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
BDNF mimetic
neurons
peptide amphiphile
nanostructure
TrkB receptor
maturation