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EURONEUROTROPHIN
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      • Achilleas Gravanis
      • Ka Wan Li
      • Dame Pamela Shaw
    • Early Stage Researchers >
      • ESR1: Daniele Narducci
      • ESR2: Alessia Latorrata
      • ESR3: Athanasios-Alexandros Tsengenes
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      • ESR6: Mirjana Antonijević
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      • ESR9: Ana Aragón
      • ESR10: Débora Pita
      • ESR11: Thanasis Rogdakis
      • ESR12: Desponia Charou
      • ESR13: Evangelia Thanou
      • ESR14: Marco Destro
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New pages and updates on Wikipedia by EuroNeurotrophin

16/8/2022

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​All EuroNeurotrophin ESRs were involved in the updating of Wikipedia pages related to the project and research fields associated to Neurotrophins to ensure outcomes from the project are documented on Wikipedia and accessible to a large audience interested in the field of Neurotrophins. In groups, the ESRs identified and reviewed relevant pages which require updates and added new content to include information and outcomes resulting from the EuroNeurotrohin project. Additionally, one group of ESRs focused on the development of a new Wikipedia page dedicated to Neurotrophin mimetics as this was not available.  Below you can find the list of articles updated by our ESRs.​
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Neurotrophin 
  • Neurotrophin
  • Nerve_growth_factor
  • Brain-derived_ neurotrophic_factor

Neurotrophin Receptors 
  • Neurotrophic_factor_receptor
  • Tropomyosin_receptor_kinase_A
  • Low- affinity_nerve_ growth_factor_receptor
  • Tropomyosin_receptor_kinase_B
  • Tropomyosin_receptor_kinase_C
 
New article: Neurotrophin mimetics ​
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ENT-A010, a Novel Steroid Derivative, Displays Neuroprotective Functions and Modulates Microglial Responses

17/3/2022

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A new EuroNeurotrophin publication has been recently published in Biomolecules on ENT-A010, a Novel Steroid Derivative, Displays Neuroprotective Functions and Modulates Microglial Responses.

Abstract
Tackling neurodegeneration and neuroinflammation is particularly challenging due to the complexity of central nervous system (CNS) disorders, as well as the limited drug accessibility to the brain. The activation of tropomyosin-related kinase A (TRKA) receptor signaling by the nerve growth factor (NGF) or the neurosteroid dehydroepiandrosterone (DHEA) may combat neurodegeneration and regulate microglial function. In the present study, we synthesized a C-17-spiro-cyclopropyl DHEA derivative (ENT-A010), which was capable of activating TRKA. ENT-A010 protected PC12 cells against serum starvation-induced cell death, dorsal root ganglia (DRG) neurons against NGF deprivation-induced apoptosis and hippocampal neurons against Aβ-induced apoptosis. In addition, ENT-A010 pretreatment partially restored homeostatic features of microglia in the hippocampus of lipopolysaccharide (LPS)-treated mice, enhanced Aβ phagocytosis, and increased Ngf expression in microglia in vitro. In conclusion, the small molecule ENT-A010 elicited neuroprotective effects and modulated microglial function, thereby emerging as an interesting compound, which merits further study in the treatment of CNS disorders.

Read the full article here: https://doi.org/10.3390/biom12030424
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New publication: Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity

7/3/2022

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We are happy to share with you the newest EuroNeurotrophin publication on Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity published in the Biomedicines journal. The full article can be read open access here: www.mdpi.com/2227-9059/10/3/614/htm

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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First EuroNeurotrophin ESR successfully defends her PhD

5/1/2022

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We are happy to announce that the first EuroNeurotophin Early Stage Researcher has defended her PhD successfully. Mirjana Antonijević (ESR6) had her PhD Defence on November 30th, 2021 on her research project on In silico screening and Hit to lead development of small molecules neurotrophin receptors ligands. 

Over the course of the project Mirjana's project focused on in silico screening of UNICAEN chemical library to identify hit molecules as ligands for neurotrophin receptors. In silico data was evaluated along with a high-throughput screening of the chemical library. Selected hit molecules were subjected to the study of hit to lead optimization, with an aim to better understand the molecular patterns involved in target-ligand interactions. Additionally, these studies were expanded by the physicochemical optimization of the selected hit compounds. The final lead compounds have been fluorescently labeled for in vivo bioimaging studies.

We would like to congratulate Mirjana and wish her all the best for the future.

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EuroNeurotrophin December 2021 Newsletter

9/12/2021

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We are happy to present to you the third EuroNeurotrophin Newsletter on the latest updates and innovations related to the project, neurotrophins and neurodegenerative diseases (ND). The EuroNeurotrophin project – is a European training network for the discovery of neurotrophins small molecule mimetics as potential therapeutic agents for neurodegeneration and neuroinflammation and is currently training 14 early-stage researchers (ESRs) to develope new ND treatments. The articles available in the newsletter are listed below:
  • Neurotrophin mimetics: recent frontiers in neurodegenerative disorders 
  • Biomolecular simulations to investigate neurotrophin receptor mechanisms and interactions with neurotrophin mimetics
  • All for one and one for all; The story about multi-target directed ligands
  • EuroNeurotrophin Conference “Neurotrophic Factors and Neurodegenerative Disorders; Current Advances and Future Perspectives”

The full newsletter written by our ESRs is available online and as download on our website. Enjoy the read!
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International Conference on “Neurotrophic Factors and Neurodegenerative Disorders; Current Advances and Future Perspectives”

16/7/2021

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We kindly invite you to the conference entitled “Neurotrophic Factors and Neurodegenerative Disorders; Current Advances and Future Perspectives” that will be organised in the context of the “EuroNeurotrophin” project by FORTH, in Crete, on August 27th-29th 2021.

The Conference will be delivered as a virtual event and registration is free of charge.
Neurodegenerative diseases (ND), like Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis and motor neuron disease, are on the rise worldwide.  Alzheimer’s disease alone affects 36 million people in the world and 7 million in Europe. The economic burden for ND exceeds 724 billion € and it will become a trillion euros by 2019. Currently, there is no cure for any ND and most of the available drugs fail to tackle ND pathogenesis.

Neurotrophins are a family of closely related secreted proteins that have been shown to control a number of aspects of survival, development and function of neurons both in the central and the peripheral nervous systems.

Preclinical studies point to the therapeutic potential of neurotrophins in preventing or slowing the progression of ND. Thus, neurotrophins have been proposed as therapeutic agents for neurodegenerative diseases.

However, the poor pharmacokinetic properties of neurotrophins, mainly because of their sensitivity to proteolysis, restricted penetration of the blood–brain barrier, and limited ability to diffuse in tissues, render their use as drugs prohibitive.

The EuroNeurotrophin project aims to address the major limitations of neurotrophins by developing novel small molecule, neurotrophin mimetics  with favourable profiles of stability, tissue penetration and targeted biological actions.

The EuroNeurotrophin project is the first European consortium to study small molecule neurotrophin mimetics (synthetic or natural) in depth, use them as molecular probes to interrogate neurotrophins, and emphasise their clinical translation.
​
Visit the conference page to register and for more details.

We look forward to seeing you online in August!


Session topics
  • In silico and structural biology studies of neurotrophin receptors
  • Medicinal Chemistry-Neurotrophin Mimetics
  • Neurotrophins and neurological diseases: from molecular mechanisms to  therapeutic potential
  • The neurogenic potential of neurotrophins
  • Novel therapeutic approaches for neurodegenerative diseases
  • Development of novel technologies for neurotrophin testing


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Virtual Training “Career path seminar on pharmaceutical industry” organised by Novartis

2/6/2021

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On the 14th May 2021 Novartis experts provided our EuroNeurotrophin ESRs a virtual seminar on “Career Paths in the Pharmaceutical Industry" to prepare them on relevant topics related to the challenges and opportunities in the pharmaceutical industry as well as what skills are required for a career in this industry.  The online seminar aim to help the ESRs to proceed with their career plans, providing interview practice and courses on topics such as CV writing.
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Interview with Susanne Kohout from Novartis

14/5/2021

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Susanne Kohout, the Country President and Managing Director of our EuroNeurotrophin Partner Organisation, Novartis (Hellas) S.A.C.I. in Greece held an interview with Fortune Greece on Novartis’ mission to help people live longer and better.

In the interview, Susanne Kohout tells us about her background and the development of the organisation and its strong position in the global market and how it got there. She also raises the concerns and challenges the COVID-19 pandemic has brought to Greece and the company itself and how they are handling this situation.

The full article is available to read online on fortunegreece.com
Novartis is ranked amongst one of the companies most heavily investing in R&D globally and we are happy to have them involved in the EuroNeurotrophin Project.

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Second EuroNeurotrophin Newsletter published

13/4/2021

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We are happy to present to you the second EuroNeurotrophin Newsletter on the latest updates and innovations related to the project, neurotrophins and neurodegenerative diseases (ND). The full newsletter written by our ESRs is available online and as download on our website. The articles available in the newsletter are listed below:
  • Computer-Aided Drug Design in the EuroNeurotrophin Project
  • Structural Biology for Neurodegenerative Diseases
  • The marine environment: a challenging source of novel drugs against neurodegeneration
  • Alzheimer’s Disease: Current therapies and future directions
  • Improving drug development for Alzheimer’s disease and other neurodegenerative diseases by using human induced stem cells
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Flash poster presentation at the Synthesis in Drug Discovery and Development Virtual Symposium

30/3/2021

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Alessia Latorrata (ESR2) presented the research from her individual research project during the Synthesis in Drug Discovery and Development Virtual Symposium, 22.-23. March. Her poster titled ”Synthesis of new DHEA 17-spyro-cyclopropyl derivatives with Neurotrophic, Neuroprotective and Anti-Inflammatory activity” was presented during the virtual poster sessions to chemists from industry and academia, including synthetic, medicinal and process chemists.

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 765704
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      • ESR3: Athanasios-Alexandros Tsengenes
      • ESR4: Christina Athanasiou
      • ESR5: Federica Carucci
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      • ESR8: Canelif Yilmaz
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