| |  Online-Ressource |
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| Verfasst von: | Rogdakis, Thanasis [VerfasserIn]  |
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| | Charou, Despoina [VerfasserIn] |
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| | Latorrata, Alessia [VerfasserIn] |
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| | Papadimitriou, Eleni [VerfasserIn] |
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| | Tsengenes, Alexandros [VerfasserIn] |
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| | Athanasiou, Christina [VerfasserIn] |
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| | Papadopoulou, Marianna [VerfasserIn] |
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| | Chalikiopoulou, Constantina [VerfasserIn] |
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| | Katsila, Theodora [VerfasserIn] |
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| | Ramos, Isbaal [VerfasserIn] |
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| | Prousis, Kyriakos C. [VerfasserIn] |
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| | Wade, Rebecca C. [VerfasserIn] |
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| | Sidiropoulou, Kyriaki [VerfasserIn] |
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| | Calogeropoulou, Theodora [VerfasserIn] |
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| | Gravanis, Achille [VerfasserIn] |
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| | Charalampopoulos, Ioannis [VerfasserIn] |
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| Titel: | Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity |
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| Verf.angabe: | Thanasis Rogdakis, Despoina Charou, Alessia Latorrata, Eleni Papadimitriou, Alexandros Tsengenes, Christina Athanasiou, Marianna Papadopoulou, Constantina Chalikiopoulou, Theodora Katsila, Isbaal Ramos, Kyriakos C. Prousis, Rebecca C. Wade, Kyriaki Sidiropoulou, Theodora Calogeropoulou, Achille Gravanis and Ioannis Charalampopoulos |
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| E-Jahr: | 2022 |
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| Jahr: | 6 March 2022 |
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| Umfang: | 27 S. |
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| Fussnoten: | Published: 6 March 2022 ; Gesehen am 27.09.2022 |
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| Titel Quelle: | Enthalten in: Biomedicines |
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| Ort Quelle: | Basel : MDPI, 2013 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 10(2022), 3, Artikel-ID 614, Seite 1-27 |
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| ISSN Quelle: | 2227-9059 |
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| Abstract: | Neurotrophins are growth factors that exert important neuroprotective effects by preventing neuronal death and synaptic loss. Nerve Growth Factor (NGF) acts through the activation of its high-affinity, pro-survival TrkA and low-affinity, pro-apoptotic p75NTR receptors. NGF has been shown to slow or prevent neurodegenerative signals in Alzheimer’s Disease (AD) progression. However, its low bioavailability and its blood-brain-barrier impermeability limit the use of NGF as a potential therapeutic agent against AD. Based on our previous findings on synthetic dehydroepiandrosterone derivatives, we identified a novel NGF mimetic, named ENT-A013, which selectively activates TrkA and exerts neuroprotective, anti-amyloid-β actions. We now report the chemical synthesis, in silico modelling, metabolic stability, CYP-mediated reaction phenotyping and biological characterization of ENT-A013 under physiological and neurodegenerative conditions. We show that ENT-A013 selectively activates the TrkA receptor and its downstream kinases Akt and Erk1/2 in PC12 cells, protecting these cells from serum deprivation-induced cell death. Moreover, ENT-A013 promotes survival of primary Dorsal Root Ganglion (DRG) neurons upon NGF withdrawal and protects hippocampal neurons against Amyloid β-induced apoptosis and synaptic loss. Furthermore, this neurotrophin mimetic partially restores LTP impairment. In conclusion, ENT-A013 represents a promising new lead molecule for developing therapeutics against neurodegenerative disorders, such as Alzheimer’s Disease, selectively targeting TrkA-mediated pro-survival signals. |
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| DOI: | doi:10.3390/biomedicines10030614 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext ; Verlag: https://doi.org/10.3390/biomedicines10030614 |
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| | kostenfrei: Volltext: https://www.mdpi.com/2227-9059/10/3/614 |
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| | DOI: https://doi.org/10.3390/biomedicines10030614 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Alzheimer disease |
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| | amyloid-beta |
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| | LTP |
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| | nerve growth factor |
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| | neuronal survival |
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| | neurotrophin |
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| | neurotrophin mimetic |
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| | synapse |
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| | TrkA neurotrophin receptor |
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| K10plus-PPN: | 181759396X |
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| Verknüpfungen: | → Zeitschrift |
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Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity / Rogdakis, Thanasis [VerfasserIn]; 6 March 2022 (Online-Ressource)
