ArticleJournal of biomedical science2015
Dimeric dipeptide mimetics of the nerve growth factor Loop 4 and Loop 1 activate TRKA with different patterns of intracellular signal transduction.
Article in Journal of biomedical science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 54 citations in OpenAlex.
- N-Isocaproyl-L-Arginylglycine Hexamethylenediamide, First Low-Molecular-Weight Mimetic of Neurotrophin-4: Design and Neuroprotective Activity.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2026Article
- Trk Signaling Inhibition Reduces cSCC Growth and Invasion in In Vitro and Zebrafish Models and Enhances Photodynamic Therapy Outcome.International journal of molecular sciences · 2025Article
- Study of the Pharmacological Activity Spectrum of the New Original NT-3 Mimetic Dipeptide GTS-302.Doklady. Biochemistry and biophysics · 2025Article
- Antidepressant-like Effects of BDNF and NGF Individual Loop Dipeptide Mimetics Depend on the Signal Transmission Patterns Associated with Trk.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
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- Peptides Derived from Growth Factors to Treat Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Dipeptide Mimetics of Different NGF and BDNF Loops Activate PLC-γ1.Doklady. Biochemistry and biophysics · 2020Article
- Identification of amino acid residues of nerve growth factor important for neurite outgrowth in human dorsal root ganglion neurons.The European journal of neuroscience · 2019Article
- Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF.Frontiers in neuroscience · 2019Review
- A novel dimeric dipeptide mimetic of the BDNF selectively activates the MAPK-Erk signaling pathway.Doklady. Biochemistry and biophysics · 2017Article
- Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK mitogen-activated protein kinase (MAPK) mechanism in mouse brain.The Journal of biological chemistry · 2017Article
- Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats.Drug design, development and therapy · 2016Article
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Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis study aimed at developing nerve growth factor (NGF) mimetics that selectively activate specific biological signals and, as a result, lack the side effects of the full-length protein. Two dimeric dipeptides, bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide (GK-6) and bis(N-succinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2), were designed based on the most exposed outside fragments of NGF, namely, the loop 1 and loop 4 β-turn sequences, respectively. These dipeptides exhibited neuroprotective activity in vitro at micro-nanomolar concentrations.
resultsStudies on the mechanism of action revealed that both compounds elevate the level of tyrosine kinase A (TrkA) receptor phosphorylation and that they each have different postreceptor signaling patterns. GK-6 increases the levels of extracellular signal-regulated kinase (ERK) and AKT kinase phosphorylation, whereas GK-2 only increases the level of AKT phosphorylation. Apart from the neuroprotective activity, GK-6 promoted differentiation in PC12 cells, whereas GK-2 did not. Furthermore, it was established that the neuroprotective activity of GK-2 was completely abolished by a selective inhibitor of phosphatidylinositol 3-kinase (LY294002) but not by a specific inhibitor of mitogen-activated protein kinases MEK1 and MEK2 (PD98059). In vivo experiments demonstrated that GK-2 did not induce hyperalgesia, which is one of the primary adverse effects of NGF. By contrast, GK-6 produced a significant decrease in the pain threshold of rats as determined by the tail flick test.
conclusionThe data obtained suggest that dimeric dipeptide NGF mimetics are promising candidates in the development of pharmacological agents with NGF-like activity that are free of the main side effect of NGF.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.