The relationships between the diverse pharmacological activities of NGF, BDNF, and NT-3 dipeptide mimetics, their patterns of post-receptor signaling activation, and the nature of the parent neurotrophins
Activation patterns of post-receptor signaling pathways of Trk receptors by dipeptide mimetics of neurotrophins
Parent neurotrophins
NGF
BDNF
NT-3
NGF
BDNF
BDNF
NT-3
Dipeptide mimetic
GTS-115
GK-61
GSB-106
GTS-302
GK-2
GSB-214
GTS-201
GTS-301
Neuroprotective activity
In vitro
+
+
+
+
+
+
+
+
In vivo
+
ns
++
+
++
+
ns
ns
Antidiabetic activity
Not assessed
Not assessed
+
Not assessed
++
++
ns
+
Memory-enhancing activity
Not assessed
ns
ns
+
+
+
ns
+
Antidepressant-like
Not assessed
+
++
++
+
+
ns
+
Anxiolytic activity
Not assessed
not assessed
+
+
Not assessed
ns
+
ns
Effect on pain sensitivity
Not assessed
↑
↓
↓
↓
ns
Not assessed
↓
NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; ns: non significant; GK-2: bis-(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide; GK-6: bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide; GTS-115: bis-(N-gamma-oxybutyryl-L-lysyl-L-histidine) hexamethylenediamide; GSB-106: bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide; GSB-214: bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide; GTS-201: bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide; GTS-301: bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) hexamethylenediamide; GTS-302: bis-(N-gamma-oxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide. All effects not labeled as “ns” are statistically significant. ↑: increase in pain thresholds; ↓: decrease in pain thresholds; 1 Although NGF mimetics GTS-115 and GK-6 both activated all major post-receptor signaling cascades of Trk receptors, GK-6, in contrast to GTS-115, induced only short-term activation of the PI3K/Akt pathway. This presumably explains the lack of neuroprotective activity of GK-6 in vivo
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Funding
This work was conducted under the government contracts of the Ministry of Science and Higher Education of the Russian Federation [FGFG-2025-0006 and FGFG-2025-0008]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Bothwell M. NGF, BDNF, NT3, and NT4.Handb Exp Pharmacol. 2014;220:3–15. [DOI] [PubMed]
Skaper SD. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors.CNS Neurol Disord Drug Targets. 2008;7:46–62. [DOI] [PubMed]
Battaglioni S, Benjamin D, Wälchli M, Maier T, Hall MN. mTOR substrate phosphorylation in growth control.Cell. 2022;185:1814–36. [DOI] [PubMed]
V AK, Mohan AS, Chakravarty S. Rapid acting antidepressants in the mTOR pathway: Current evidence.Brain Res Bull. 2020;163:170–77. [DOI] [PubMed]
Indrigo M, Morella I, Orellana D, d'Isa R, Papale A, Parra R, et al. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.EMBO Mol Med. 2023;15:e15984. [DOI] [PubMed] [PMC]
Sun J, Nan G. The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target (Review).Int J Mol Med. 2017;39:1338–46. [DOI] [PubMed] [PMC]
Schevzov G, Kee AJ, Wang B, Sequeira VB, Hook J, Coombes JD, et al. Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments.Mol Biol Cell. 2015;26:2475–90. [DOI] [PubMed] [PMC]
Lee S, Kim C, Shin M, Lim B. Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils.J Exerc Rehabil. 2020;16:49–57. [DOI] [PubMed] [PMC]
Belgacem YH, Borodinsky LN. CREB at the Crossroads of Activity-Dependent Regulation of Nervous System Development and Function.Adv Exp Med Biol. 2017;1015:19–39. [DOI] [PubMed]
Mai L, Zhu X, Huang F, He H, Fan W. p38 mitogen-activated protein kinase and pain.Life Sci. 2020;256:117885. [DOI] [PubMed]
Barford K, Deppmann C, Winckler B. The neurotrophin receptor signaling endosome: Where trafficking meets signaling.Dev Neurobiol. 2017;77:405–18. [DOI] [PubMed] [PMC]
Alfonsetti M, d'Angelo M, Castelli V. Neurotrophic factor-based pharmacological approaches in neurological disorders.Neural Regen Res. 2023;18:1220–8. [DOI] [PubMed] [PMC]
Gliwińska A, Czubilińska-Łada J, Więckiewicz G, Świętochowska E, Badeński A, Dworak M, et al. The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer's Disease as Highly Drug-Resistant Diseases: A Narrative Review.Brain Sci. 2023;13:163. [DOI] [PubMed] [PMC]
Rocco ML, Soligo M, Manni L, Aloe L. Nerve Growth Factor: Early Studies and Recent Clinical Trials.Curr Neuropharmacol. 2018;16:1455–65. [DOI] [PubMed] [PMC]
Jaiswal A, Shreekantiah U, Goyal N. Nerve Growth Factor in Psychiatric Disorders: A Scoping Review.Indian J Psychol Med. 2023;45:555–64. [DOI] [PubMed] [PMC]
Miranda ASd, Barros JLVMd, Teixeira AL. Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?Expert Opin Ther Targets. 2020;24:1225–38. [DOI] [PubMed]
Merighi A. Brain-Derived Neurotrophic Factor, Nociception, and Pain.Biomolecules. 2024;14:539. [DOI] [PubMed] [PMC]
Xhima K, Markham-Coultes K, Kofoed RH, Saragovi HU, Hynynen K, Aubert I. Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies.Brain. 2022;145:2806–22. [DOI] [PubMed] [PMC]
Longo FM, Massa SM. Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease.Nat Rev Drug Discov. 2013;12:507–25. [DOI] [PubMed]
Travaglia A, Pietropaolo A, Martino RD, Nicoletti VG, Mendola DL, Calissano P, et al. A small linear peptide encompassing the NGF N-terminus partly mimics the biological activities of the entire neurotrophin in PC12 cells.ACS Chem Neurosci. 2015;6:1379–92. [DOI] [PubMed]
Fletcher JL, Wood RJ, Nguyen J, Norman EML, Jun CMK, Prawdiuk AR, et al. Targeting TrkB with a Brain-Derived Neurotrophic Factor Mimetic Promotes Myelin Repair in the Brain.J Neurosci. 2018;38:7088–99. [DOI] [PubMed] [PMC]
Chen D, Brahimi F, Angell Y, Li Y, Moscowicz J, Saragovi HU, et al. Bivalent peptidomimetic ligands of TrkC are biased agonists and selectively induce neuritogenesis or potentiate neurotrophin-3 trophic signals.ACS Chem Biol. 2009;4:769–81. [DOI] [PubMed] [PMC]
Zaccaro MC, Lee HB, Pattarawarapan M, Xia Z, Caron A, L'Heureux P, et al. Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities.Chem Biol. 2005;12:1015–28. [DOI] [PubMed]
Sidorova YA, Volcho KP, Salakhutdinov NF. Neuroregeneration in Parkinson's Disease: From Proteins to Small Molecules.Curr Neuropharmacol. 2019;17:268–87. [DOI] [PubMed] [PMC]
Nguyen TV, Shen L, Griend LV, Quach LN, Belichenko NP, Saw N, et al. Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AβPPL/S transgenic mice.J Alzheimers Dis. 2014;42:459–83. [DOI] [PubMed] [PMC]
Simmons DA, Knowles JK, Belichenko NP, Banerjee G, Finkle C, Massa SM, et al. A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression.PLoS One. 2014;9:e102136. [DOI] [PubMed] [PMC]
Dahlström M, Madjid N, Nordvall G, Halldin MM, Vazquez-Juarez E, Lindskog M, et al. Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction.Cells. 2021;10:1871. [DOI] [PubMed] [PMC]
Fernandez CP, Juric S, Backlund M, Dahlström M, Madjid N, Lidell V, et al. Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.Int J Mol Sci. 2023;24:11159. [DOI] [PubMed] [PMC]
Gudasheva TA, Antipova TA, Seredenin SB. Novel low-molecular-weight mimetics of the nerve growth factor.Dokl Biochem Biophys. 2010;434:262–5. [DOI] [PubMed]
Gudasheva TA, Tarasiuk AV, Pomogaĭbo SV, Logvinov IO, Povarnina PI, Antipova TA, et al. Design and synthesis of dipeptide mimetics of the brain-derived neurotrophic factor.Bioorg Khim. 2012;38:280–90. [DOI] [PubMed]
Gudasheva TA, Povarnina PY, Tarasiuk AV, Seredenin SB. Low-molecular mimetics of nerve growth factor and brain-derived neurotrophic factor: Design and pharmacological properties.Med Res Rev. 2021;41:2746–74. [DOI] [PubMed]
Gudasheva TA, Sazonova NM, Tarasiuk AV, Logvinov IO, Antipova TA, Nikiforov DM, et al. The First Dipeptide Mimetic of Neurotrofin-3: Design and Pharmacological Properties.Dokl Biochem Biophys. 2022;505:160–5. [DOI] [PubMed]
Gudasheva TA, Tarasiuk AV, Sazonova NM, Pomogaibo SV, Shumskiy AN, Logvinov IO, et al. Design, synthesis, and neuroprotective effects of a dimeric dipeptide mimetic of the third loop of the nerve growth factor.Bioorg Khim. 2017;43:235–47. Russian. [DOI]
Gudasheva TA, Tarasiuk AV, Sazonova NM, Povarnina PY, Antipova TA, Seredenin SB. A novel dimeric dipeptide mimetic of the BDNF selectively activates the MAPK-Erk signaling pathway.Dokl Biochem Biophys. 2017;476:291–5. [DOI] [PubMed]
Tarasiuk AV, Sazonova NM, Melnikova MV, Pomogaybo SV, Logvinov IO, Nikolaev SV, et al. Design and synthesis of a novel dipeptide mimetic of the 4th loop of neurotrophin-3 and its pharmacological effects.Mendeleev Communications. 2023; 33:786–9. [DOI]
Gudasheva TA, Povarnina PY, Antipova TA, Firsova YN, Konstantinopolsky MA, Seredenin SB. Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction.J Biomed Sci. 2015;22:106. [DOI] [PubMed] [PMC]
Gudasheva TA, Povarnina P, Logvinov IO, Antipova TA, Seredenin SB. Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats.Drug Des Devel Ther. 2016;10:3545–53. [DOI] [PubMed] [PMC]
Antipova TA, Deev IE, Gudasheva TA, Serova OV, Gavrilenkova AA, Povarnina PYu, et al. Evidence of Selective Interaction of Nerve Growth Factor Dipeptide Mimetic GK-2 with TrkA Receptor Using TrkA and TrkB Knockout HT-22 Cells.Pharmaceutical Chemistry Journal. 2023;56:1568–72. [DOI]
Antipova TA, Logvinov IO, Deyev IE, Povarnina PY, Vakhitova YV, Gudasheva TA, et al. Pharmacogenetic Analysis of the Interaction of the Low-Molecular-Weight BDNF Mimetic Dipeptide GSB-106 with TRK Receptors.Dokl Biochem Biophys. 2023;511:166–8. [DOI] [PubMed]
Gudasheva TA, Logvinov IO, Nikolaev SV, Antipova TA, Povarnina PY, Seredenin SB. Dipeptide Mimetics of Different NGF and BDNF Loops Activate PLC-γ1.Dokl Biochem Biophys. 2020;494:244–7. [DOI] [PubMed]
Kolik LG, Konstantinipolsky MA, Nikolaev SV, Logvinov IO, Antipova TA, Gudasheva TA. Low-Molecular Neurotrophin-3 Mimetics with Different Patterns of Postreceptor Signaling Activation Attenuate Differentially Morphine Withdrawal in Rats.Biochemistry (Mosc). 2024;89:1961–9. [DOI] [PubMed]
Nikiforov DM, Povarnina PY, Gudasheva TA, Nadorova AV, Kolik LG, Valdman EA, et al. Study of the Pharmacological Activity Spectrum of the New Original NT-3 Mimetic Dipeptide GTS-302.Dokl Biochem Biophys. 2025;23:87–99. Russian. [DOI] [PubMed]
Zainullina LF, Vakhitova YV, Lusta AY, Gudasheva TA, Seredenin SB. Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression.Sci Rep. 2021;11:7781. [DOI] [PubMed] [PMC]
Encinas M, Iglesias M, Llecha N, Comella JX. Extracellular-regulated kinases and phosphatidylinositol 3-kinase are involved in brain-derived neurotrophic factor-mediated survival and neuritogenesis of the neuroblastoma cell line SH-SY5Y.J Neurochem. 1999;73:1409–21. [DOI] [PubMed]
Povarnina PY, Antipova TA, Gudasheva TA, Seredenin SB. Neuroprotective and Neuroregenerative Properties of Dimeric Dipeptide Mimetics of Individual NGF and BDNF Loops Under Conditions of an Experimental Ischemic Stroke Model.Pharm Chem J. 2022;56:1019–23. [DOI]
Xiao C, Yin W, Zhong Y, Luo J, Liu L, Liu W, et al. The role of PI3K/Akt signalling pathway in spinal cord injury.Biomed Pharmacother. 2022;156:113881. [DOI] [PubMed]
Goyal A, Agrawal A, Verma A, Dubey N. The PI3K-AKT pathway: A plausible therapeutic target in Parkinson's disease.Exp Mol Pathol. 2023;129:104846. [DOI] [PubMed]
Khan H, Singh A, Thapa K, Garg N, Grewal AK, Singh TG. Therapeutic modulation of the phosphatidylinositol 3-kinases (PI3K) pathway in cerebral ischemic injury.Brain Res. 2021;1761:147399. [DOI] [PubMed]
Gugliandolo A, Silvestro S, Sindona C, Bramanti P, Mazzon E. MiRNA: Involvement of the MAPK Pathway in Ischemic Stroke. A Promising Therapeutic Target.Medicina (Kaunas). 2021;57:1053. [DOI] [PubMed] [PMC]
Schanbacher C, Bieber M, Reinders Y, Cherpokova D, Teichert C, Nieswandt B, et al. ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke.Int J Mol Sci. 2022;23:706. [DOI] [PubMed] [PMC]
Chiu Y, Lin T, Chang K, Lin W, Hsieh-Li HM, Su M, et al. Novel TRKB agonists activate TRKB and downstream ERK and AKT signaling to protect Aβ-GFP SH-SY5Y cells against Aβ toxicity.Aging (Albany NY). 2022;14:7568–86. [DOI] [PubMed] [PMC]
Ostrovskaya RU, Yagubova SS, Gudasheva TA, Seredenin SB. Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways.Bull Exp Biol Med. 2018;164:734–7. [DOI] [PubMed]
Yagubova SS, Chernyshevskaya MA, Ostrovskaya RU, Gudasheva TA, Seredenin SB. Antidiabetic Effect of a New Original NT-3 Dipeptide Mimetic.Dokl Biochem Biophys. 2023;512:241–4. [DOI] [PubMed]
Ivanov SV, Ostrovskaya RU, Khlybova AS, Gudasheva TA. Low-Molecular-Weight Perorally Active Nerve Growth Factor Mimetic Reduces Manifestations of Diabetic Neuropathy in Wistar Rats.Bull Exp Biol Med. 2022;173:37–40. [DOI] [PubMed]
Yagubova SS, Ostrovskaya RU, Gudasheva TA, Seredenin SB. Dipeptide mimetic of nerve growth factor GK-2 retains the antidiabetic activity upon intraperitoneal and oral administration in mice.Exp Clin Pharmacol. 2017;80:23–6. Russian.
Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB β.J Clin Invest. 2003;112:197–208. [DOI] [PubMed] [PMC]
Elghazi L, Rachdi L, Weiss AJ, Cras-Méneur C, Bernal-Mizrachi E. Regulation of β-cell mass and function by the Akt/protein kinase B signalling pathway.Diabetes Obes Metab. 2007;9:147–57. [DOI] [PubMed]
Ostrovskaya RU, Ivanov SV. Neuroprotective Substances: Are they Able to Protect the Pancreatic Beta- Cells Too?Endocr Metab Immune Disord Drug Targets. 2022;22:834–41. [DOI] [PubMed]
Yagubova SS, Ostrovskaya RU, Gudasheva TA, Seredenin SB. The PI3K/Akt Cascade Is Involved in the Antidiabetic Effect of Compound GSB-214, a Low-Molecular-Weight BDNF Mimetic.Bull Exp Biol Med. 2020;169:771–4. [DOI] [PubMed]
Yagubova SS, Zolotov NN, Ostrovskaya RU, Gudasheva TA. Analysis of the Role of PI3K/Akt Pathway in the Realization of the Normalizing Effect of Low-Molecular-Weight Mimetics of NGF and BDNF on Activity of Prooxidant and Antioxidant Systems in C57BL/6 Mice with Modeled Diabetes.Bull Exp Biol Med. 2022;174:273–6. [DOI] [PubMed]
Polyakova M, Stuke K, Schuemberg K, Mueller K, Schoenknecht P, Schroeter ML. BDNF as a biomarker for successful treatment of mood disorders: a systematic & quantitative meta-analysis.J Affect Disord. 2015;174:432–40. [DOI] [PubMed]
Mondal AC, Fatima M. Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment.Int J Neurosci. 2019;129:283–96. [DOI] [PubMed]
Banerjee R, Ghosh AK, Ghosh B, Bhattacharyya S, Mondal AC. Decreased mRNA and Protein Expression of BDNF, NGF, and their Receptors in the Hippocampus from Suicide: An Analysis in Human Postmortem Brain.Clin Med Insights Pathol. 2013;6:1–11. [PubMed] [PMC]
Shatri H, Pranandi M, Ardani Y, Firmansyah I, Faisal E, Putranto R. The role of Neurotrophin 3 (NT-3) on neural plasticity in depression: a literature review.Intisari Sains Medis. 2023;14:1103–8. [DOI]
Ogłodek EA, Just MJ, Szromek AR, Araszkiewicz A. Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity.Pharmacol Rep. 2016;68:945–51. [DOI] [PubMed]
Mezhlumyan AG, Tallerova AV, Povarnina PY, Tarasiuk AV, Sazonova NM, Gudasheva TA, et al. Antidepressant-like Effects of BDNF and NGF Individual Loop Dipeptide Mimetics Depend on the Signal Transmission Patterns Associated with Trk.Pharmaceuticals (Basel). 2022;15:284. [DOI] [PubMed] [PMC]
Overstreet DH, Fredericks K, Knapp D, Breese G, McMichael J. Nerve growth factor (NGF) has novel antidepressant-like properties in rats.Pharmacol Biochem Behav. 2010;94:553–60. [DOI] [PubMed] [PMC]
Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression.J Neurosci. 2002;22:3251–61. [DOI] [PubMed] [PMC]
Gudasheva TA, Tallerova AV, Mezhlumyan AG, Antipova TA, Logvinov IO, Firsova YN, et al. Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress.Biomolecules. 2021;11:252. [DOI] [PubMed] [PMC]
Kim J, Kaang B. Cyclic AMP response element-binding protein (CREB) transcription factor in astrocytic synaptic communication.Front Synaptic Neurosci. 2023;14:1059918. [DOI] [PubMed] [PMC]
Povarnina PY, Nikiforov DM, Antipova TA, Logvinov IO. The Dipeptide Mimetic of the Compound GTS-302, Exhibits Antidepressant-Like Activity in a Mouse Social Defeat Stress Model.Int J Med Front. 2024;7:1–9.
Yin X, Ma Y, Liu Y, Wang L, Du N, Yang L. Changes of brain-derived neurotrophic factors in rats with generalized anxiety disorder before and after treatment.Eur Rev Med Pharmacol Sci. 2022;26:1500–7. [DOI] [PubMed]
Shafiee A, Jafarabady K, Mohammadi I, Rajai S. Brain-derived neurotrophic factor (BDNF) levels in panic disorder: A systematic review and meta-analysis.Brain Behav. 2024;14:e3349. [DOI] [PubMed] [PMC]
Kolik LG, Nadorova AV, Grigorevskikh EM, Gudasheva TA, Seredenin SB. Experimental study of the anxiolytic activity of low-molecular-mass mimetics of the first, second and fourth loops of brain derived neurotrophic factor.Exp Clin Pharmacol. 2020;83:3–7. Russian.
Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain.Front Cell Neurosci. 2019;13:363. [DOI] [PubMed] [PMC]
Eu WZ, Chen Y, Chen W, Wu K, Tsai C, Cheng S, et al. The effect of nerve growth factor on supporting spatial memory depends upon hippocampal cholinergic innervation.Transl Psychiatry. 2021;11:162. [DOI] [PubMed] [PMC]
Shimazu K, Zhao M, Sakata K, Akbarian S, Bates B, Jaenisch R, et al. NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis.Learn Mem. 2006;13:307–15. [DOI] [PubMed] [PMC]
Volkova AA, Povarnina PY, Nikiforov DM, Gudasheva TA, Seredenin SB. Comparative Study of the Mnemotropic Activity of Dimeric Dipeptide Mimetics of Individual NGF and BDNF Loops Using a New-Object Recognition Test in Rats.Pharm Chem J. 2022;56:429–32. [DOI]
Wang S, Liao X, Liu D, Hu J, Yin Y, Wang J, et al. NGF promotes long-term memory formation by activating poly(ADP-ribose)polymerase-1.Neuropharmacology. 2012;63:1085–92. [DOI] [PubMed]
Birch AM, Kelly ÁM. Chronic intracerebroventricular infusion of nerve growth factor improves recognition memory in the rat.Neuropharmacology. 2013;75:255–61. [DOI] [PubMed]
Bechara RG, Lyne R, Kelly ÁM. BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat.Behav Brain Res. 2014;275:297–306. [DOI] [PubMed]
Callaghan CK, Kelly AM. Neurotrophins play differential roles in short and long-term recognition memory.Neurobiol Learn Mem. 2013;104:39–48. [DOI] [PubMed]
Bockaert J, Marin P. mTOR in Brain Physiology and Pathologies.Physiol Rev. 2015;95:1157–87. [DOI] [PubMed]
Medina JH, Viola H. ERK1/2: A Key Cellular Component for the Formation, Retrieval, Reconsolidation and Persistence of Memory.Front Mol Neurosci. 2018;11:361. [DOI] [PubMed] [PMC]
Barker PA, Mantyh P, Arendt-Nielsen L, Viktrup L, Tive L. Nerve Growth Factor Signaling and Its Contribution to Pain.J Pain Res. 2020;13:1223–41. [DOI] [PubMed] [PMC]
Xiong HY, Hendrix J, Schabrun S, Wyns A, Campenhout JV, Nijs J, et al. The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.Biomolecules. 2024;14:71. [DOI] [PubMed] [PMC]
Siuciak JA, Altar CA, Wiegand SJ, Lindsay RM. Antinociceptive effect of brain-derived neurotrophic factor and neurotrophin-3.Brain Res. 1994;633:326–30. [DOI] [PubMed]
Siuciak JA, Wong V, Pearsall D, Wiegand SJ, Lindsay RM. BDNF produces analgesia in the formalin test and modifies neuropeptide levels in rat brain and spinal cord areas associated with nociception.Eur J Neurosci. 1995;7:663–70. [DOI] [PubMed]
Boakye PA, Rancic V, Whitlock KH, Simmons D, Longo FM, Ballanyi K, et al. Receptor dependence of BDNF actions in superficial dorsal horn: relation to central sensitization and actions of macrophage colony stimulating factor 1.J Neurophysiol. 2019;121:2308–22. [DOI] [PubMed]
M'Dahoma S, Barthélemy S, Tromilin C, Jeanson T, Viguier F, Michot B, et al. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats.Eur Neuropsychopharmacol. 2015;25:2118–30. [DOI] [PubMed]
Watanabe M, Endo Y, Kimoto K, Katoh-Semba R, Arakawa Y. Inhibition of adjuvant-induced inflammatory hyperalgesia in rats by local injection of neurotrophin-3.Neurosci Lett. 2000;282:61–4. [DOI] [PubMed]
Zhou XF, Deng YS, Xian CJ, Zhong JH. Neurotrophins from dorsal root ganglia trigger allodynia after spinal nerve injury in rats.Eur J Neurosci. 2000;12:100–5. [DOI] [PubMed]
Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity.Life Sci. 2004;74:2643–53. [DOI] [PubMed]
Capsoni S, Covaceuszach S, Marinelli S, Ceci M, Bernardo A, Minghetti L, et al. Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity.PLoS One. 2011;6:e17321. [DOI] [PubMed] [PMC]
Gudasheva TA, Konstantinopolsky MA, Tarasiuk AV, Kolik LG, Seredenin SB. Dipeptide Mimetic of the BDNF Loop 4 Possesses Analgetic Activity.Dokl Biochem Biophys. 2019;485:123–5. [DOI] [PubMed]
Cárdenas C, Santana P, Álvarez C, Mercado L, Marshall S, Albericio F, et al. Synthetic peptides as valuable and versatile tools for research: our 20 year journey in Chile.Explor Drug Sci. 2024;2:701–18. [DOI]
