Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
6 March 2022
|
| In: |
Biomedicines
Year: 2022, Volume: 10, Issue: 3, Pages: 1-27 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines10030614 |
| Online Access: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.3390/biomedicines10030614 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2227-9059/10/3/614 
|
| Author Notes: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 181759396X | ||
| 003 | DE-627 | ||
| 005 | 20230426141044.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220927s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/biomedicines10030614 |2 doi | |
| 035 | |a (DE-627)181759396X | ||
| 035 | |a (DE-599)KXP181759396X | ||
| 035 | |a (OCoLC)1361696185 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Rogdakis, Thanasis |e VerfasserIn |0 (DE-588)1268964026 |0 (DE-627)1817596470 |4 aut | |
| 245 | 1 | 0 | |a Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity |c 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 |
| 264 | 1 | |c 6 March 2022 | |
| 300 | |a 27 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published: 6 March 2022 | ||
| 500 | |a Gesehen am 27.09.2022 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Alzheimer disease | |
| 650 | 4 | |a amyloid-beta | |
| 650 | 4 | |a LTP | |
| 650 | 4 | |a nerve growth factor | |
| 650 | 4 | |a neuronal survival | |
| 650 | 4 | |a neurotrophin | |
| 650 | 4 | |a neurotrophin mimetic | |
| 650 | 4 | |a synapse | |
| 650 | 4 | |a TrkA neurotrophin receptor | |
| 700 | 1 | |a Charou, Despoina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Latorrata, Alessia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Papadimitriou, Eleni |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tsengenes, Alexandros |d 1993- |e VerfasserIn |0 (DE-588)1269014579 |0 (DE-627)1817668854 |4 aut | |
| 700 | 1 | |a Athanasiou, Christina |d 1993- |e VerfasserIn |0 (DE-588)1269014919 |0 (DE-627)1817668900 |4 aut | |
| 700 | 1 | |a Papadopoulou, Marianna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chalikiopoulou, Constantina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Katsila, Theodora |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ramos, Isbaal |e VerfasserIn |4 aut | |
| 700 | 1 | |a Prousis, Kyriakos C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wade, Rebecca C. |e VerfasserIn |0 (DE-588)102801774X |0 (DE-627)730136000 |0 (DE-576)276591402 |4 aut | |
| 700 | 1 | |a Sidiropoulou, Kyriaki |e VerfasserIn |4 aut | |
| 700 | 1 | |a Calogeropoulou, Theodora |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gravanis, Achille |e VerfasserIn |4 aut | |
| 700 | 1 | |a Charalampopoulos, Ioannis |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biomedicines |d Basel : MDPI, 2013 |g 10(2022), 3, Artikel-ID 614, Seite 1-27 |h Online-Ressource |w (DE-627)750370483 |w (DE-600)2720867-9 |w (DE-576)384589596 |x 2227-9059 |7 nnas |a Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity |
| 773 | 1 | 8 | |g volume:10 |g year:2022 |g number:3 |g elocationid:614 |g pages:1-27 |g extent:27 |a Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity |
| 856 | 4 | 0 | |u https://doi.org/10.3390/biomedicines10030614 |x Resolving-System |x Verlag |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.mdpi.com/2227-9059/10/3/614 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220927 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 102801774X |a Wade, Rebecca C. |m 102801774X:Wade, Rebecca C. |d 140000 |e 140000PW102801774X |k 0/140000/ |p 12 | ||
| 998 | |g 1269014919 |a Athanasiou, Christina |m 1269014919:Athanasiou, Christina |d 140000 |e 140000PA1269014919 |k 0/140000/ |p 6 | ||
| 998 | |g 1269014579 |a Tsengenes, Alexandros |m 1269014579:Tsengenes, Alexandros |d 140000 |e 140000PT1269014579 |k 0/140000/ |p 5 | ||
| 999 | |a KXP-PPN181759396X |e 4192388103 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"note":["Gesehen am 12.08.20"],"type":{"media":"Online-Ressource","bibl":"periodical"},"physDesc":[{"extent":"Online-Ressource"}],"pubHistory":["1.2013 -"],"language":["eng"],"title":[{"title_sort":"Biomedicines","title":"Biomedicines","subtitle":"open access journal"}],"recId":"750370483","disp":"Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicityBiomedicines","origin":[{"publisherPlace":"Basel","publisher":"MDPI","dateIssuedKey":"2013","dateIssuedDisp":"2013-"}],"id":{"eki":["750370483"],"issn":["2227-9059"],"zdb":["2720867-9"]},"part":{"text":"10(2022), 3, Artikel-ID 614, Seite 1-27","extent":"27","pages":"1-27","volume":"10","issue":"3","year":"2022"}}],"note":["Published: 6 March 2022","Gesehen am 27.09.2022"],"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"6 March 2022"}],"id":{"eki":["181759396X"],"doi":["10.3390/biomedicines10030614"]},"recId":"181759396X","name":{"displayForm":["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"]},"title":[{"title_sort":"Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity","title":"Development and biological characterization of a novel selective TrkA agonist with neuroprotective properties against amyloid toxicity"}],"person":[{"display":"Rogdakis, Thanasis","family":"Rogdakis","given":"Thanasis","role":"aut"},{"given":"Despoina","role":"aut","family":"Charou","display":"Charou, Despoina"},{"family":"Latorrata","given":"Alessia","role":"aut","display":"Latorrata, Alessia"},{"display":"Papadimitriou, Eleni","role":"aut","given":"Eleni","family":"Papadimitriou"},{"display":"Tsengenes, Alexandros","role":"aut","given":"Alexandros","family":"Tsengenes"},{"display":"Athanasiou, Christina","role":"aut","given":"Christina","family":"Athanasiou"},{"display":"Papadopoulou, Marianna","given":"Marianna","role":"aut","family":"Papadopoulou"},{"display":"Chalikiopoulou, Constantina","family":"Chalikiopoulou","role":"aut","given":"Constantina"},{"display":"Katsila, Theodora","family":"Katsila","given":"Theodora","role":"aut"},{"display":"Ramos, Isbaal","given":"Isbaal","role":"aut","family":"Ramos"},{"family":"Prousis","given":"Kyriakos C.","role":"aut","display":"Prousis, Kyriakos C."},{"display":"Wade, Rebecca C.","family":"Wade","given":"Rebecca C.","role":"aut"},{"role":"aut","given":"Kyriaki","family":"Sidiropoulou","display":"Sidiropoulou, Kyriaki"},{"display":"Calogeropoulou, Theodora","given":"Theodora","role":"aut","family":"Calogeropoulou"},{"family":"Gravanis","role":"aut","given":"Achille","display":"Gravanis, Achille"},{"given":"Ioannis","role":"aut","family":"Charalampopoulos","display":"Charalampopoulos, Ioannis"}],"language":["eng"],"physDesc":[{"extent":"27 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"}} | ||
| SRT | |a ROGDAKISTHDEVELOPMEN6202 | ||