ArticleInternational journal of molecular sciences2015
Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its Derivatives with TrkB and VEGFR2 Proteins.
Article in International journal of molecular sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Inhibition of Vascular Endothelial Growth Factor Reduces Photoreceptor Death in Retinal Neovascular Disease via Neurotrophic Modulation in Müller Glia.Molecular neurobiology · 2025Article
- A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2024Article
- A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo.Cell communication and signaling : CCS · 2024Article
- The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Retinal vascular recovery revealed by retinal imaging following neonatal hypoxia ischemia in mice: Is there a role for tyrosine kinase receptor modulation?Brain research · 2022Article
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- 7,8-Dihydroxiflavone Protects Adult Rat Axotomized Retinal Ganglion Cells through MAPK/ERK and PI3K/AKT Activation.International journal of molecular sciences · 2021Article
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- Computational Design of Radical Recognition Assay with the Possible Application of Cyclopropyl Vinyl Sulfides as Tunable Sensors.International journal of molecular sciences · 2021Article
- Flavones 7,8-DHF, Quercetin, and Apigenin Against Tau ToxicityFrontiers in aging neuroscience · 2021Article
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- BDNF Outperforms TrkB Agonist 7,8,3'-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs.Brain sciences · 2020Article
- LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer's disease.Psychopharmacology · 2020Article
- Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLJournal of translational medicine · 2020Article
- Design and Molecular dynamic Investigations of 7,8-Dihydroxyflavone Derivatives as Potential Neuroprotective Agents Against Alpha-synuclein.Scientific reports · 2020Article
- Neuroprotection: Pro-survival and Anti-neurotoxic Mechanisms as Therapeutic Strategies in Neurodegeneration.Frontiers in cellular neuroscience · 2019Review
- Glaucoma Pathogenesis and Neurotrophins: Focus on the Molecular and Genetic Basis for Therapeutic Prospects.Current neuropharmacology · 2018Review
- Genome editing abrogates angiogenesis in vivo.Nature communications · 2017Article
- Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor.Data in brief · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
7,8-dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue.
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